The ripening process of fleshy fruits is characterized by coordinated changes in whereby fruit biochemistry and physiology are both drastically altered (Brady, 1987; Giovannoni, 2004; Giovannoni et al., 2017). These changes during ripening are typically variable according to the species and maturation stages as well as in response to stress conditions, often due to changes in secondary metabolism, thereby potentially increasing plant defenses and the concentrations of compounds involved in plant protection (Miller et al., 1998; Giovannoni, 2004; Giovannoni et al., 2017). Nevertheless, the main modifications observed during ripening are associated with color and textural alterations coupled with modifications of sugars, organic acids, and volatile compounds (Giovannoni, 2004). Altogether, such modifications contribute to fruit flavor, especially by adjusting the balance between sugar and organic acids (Chaimanee and Suntornwat, 1994). Accordingly, the major respiratory substrates present in most fruits are carbohydrates and organic acids and both their nature and concentration largely affect organoleptic quality as taste, sight, and smell (Seymour et al., 2013).

Sugar accumulation has been intensely investigated during fruit development in different species under diverse conditions. Throughout ripening the vast majority of fleshy fruits are characterized by increases in sugar contents whereas organic acids decrease (Giovannoni et al., 2017). Citrus species are the exception to this metabolic ‘rule,’ especially at the peak of maturity or ripening. Global transcriptome analysis has suggested that during middle and later stages of citrus fruit development both carbohydrate synthesis and catabolism are mostly down-regulated while sugar transport appears to be rather operative. This can be deduced from the up-regulation of sucrose phosphate synthase (SPS), which in turn is correlated with total soluble solids (TSS) and the up-regulation of citrate synthase (CS) (Cercós et al., 2006; Wang et al., 2017). In parallel with fruit growth, sugars and organic acids are accumulated but in different stages of development. Glucose, fructose and sucrose increase in an exponential manner during cell division phase, reaching stable levels during final growth and ripening process. The content of citrate, the main organic acid found in citric fruits, increases upon cell division stage reaching higher levels in the middle of stage II and decreasing, mostly due to its catabolism, during ripening (Iglesias et al., 2007; Hussain et al., 2017). Both metabolic patterns and concentration are highly variable according to the species. In this vein, accumulation of sucrose, glucose, and fructose during ripening are especially observed in sweet fruits such as apples (Jakopic et al., 2018; Williams and Benkeblia, 2018), litchi (Yang Z. et al., 2013), melons (Burger et al., 2000; Huang et al., 2017), peach (Cirilli et al., 2016), strawberries (Shanmugam et al., 2017), mango (Cosme Silva et al., 2017), papaya (Paull et al., 1999) and watermelons (Liu et al., 2013) (Table 2). In general, sugar accumulation in fruit is directly controlled by increasing the activities of sucrose synthase (Suzy) and SPS (Chen et al., 2004).

Sucrose, glucose, and fructose are the most abundant carbohydrates and widely distributed food components present in plants. Their ratios vary considerably between fruits and, to a lower extent, in the same fruit according to maturation stage (Arena et al., 2013). Notably, the oxidation of such carbohydrates via glycolysis provides substrates for the TCA cycle during cell respiratory processes, contributing not only to the generation of intermediates such as organic acids, but also contributing to cellular energy supply (Osorio et al., 2013). Remarkably, during the climacteric stage, there is a large increase in the rate of substrate oxidation, mediated mainly by mitochondrial oxidases and, as result, there is an increased glycolytic flux. Interestingly, this enhanced flux has been associated with a close relationship between the activities of key glycolytic enzymes such as pyruvate kinase and phosphofructokinase in different fruits including apple, avocado, banana, and tomato (Rhodes and Wooltorton, 1967; Bennett et al., 1987; Beauvoit et al., 2018).

Similarly to sugars, organic acids are also able to support several facets of plant metabolism. Thus, the accumulation of organic acids in plant cells is highly correlated with other metabolic pathways and appears to be under the control of many factors (Lin et al., 2016). Both the organic acid type and its levels are extremely dependent of species, development stages, and the tissue analyzed. Although changes in content of organic acids are strongly fruit-dependent the most abundant organic acids in several fruits are citrate and malate (Romero Rodriguez et al., 1992), both being variable over different stages of fruit development (Table 2). Unlike soluble carbohydrates, which are imported into the fruit as photosynthate, the majority of the organic acids present in fleshy fruits are not imported but rather synthesized in situ, mostly from imported sugars from glycolysis mediating starch and cell wall degradation (Etienne et al., 2013). This is in good agreement with findings showing that starch accumulation plays an important role in determining the soluble solids content (°Brix index) of mature fruit, which is directly influenced by the activity of invertases, such as tomato LIN5 (Schaffer and Petreikov, 1997; Vallarino et al., 2017). Therefore, organic acids appear as highly valuable metabolites from a metabolic engineering perspective, once the organic acid-to-sugar ratio defines a range of quality parameters at harvest time in fruits.

By using integrative analyses of metabolomics and transcriptome during fruit ripening in ponkan (Citrus reticulata) fruits, it was showed that increases in sugars content are followed by considerable reductions in the content of organic acids (Lin et al., 2015). Perhaps more importantly, it was demonstrated that such behavior might be driven by SPS, asparagine transferases (AST), ATP-citrate lyase and glutamate decarboxylase (GAD) mediating shifts in sucrose metabolism from synthesis to degradation, which was regulated by the balance between SPS and SuSy activity (Lin et al., 2015, 2016). In addition, increased enzyme activity from both glycolysis and the TCA cycle during later maturation were observed, indicating that the flux is somehow changing from sucrose metabolism to organic acid metabolism, with citrate degradation occurring mainly through the gamma-aminobutyric acid (GABA) and acetyl-CoA pathways (Lin et al., 2015, 2016). It was further demonstrated that ponkan fruits under hot air treatment could activate citrate degradation via the GABA shunt especially by modulating aconitase, isocitrate dehydrogenase and glutamate decarboxylase cascade, but not the glycolytic pathway (Chen et al., 2012).

Positive correlation between malate levels and the expression of genes involved in starch synthesis has been observed in pepper (Capsicum spp.) fruits, meaning that malate metabolism most likely regulates transitory starch metabolism and that this process is probably conserved between climacteric and non-climacteric fruits (Osorio et al., 2012). Indeed, reduction of the activities of either the mitochondrial malate dehydrogenase (mMDH) or fumarase (FUM) in tomato fruits via targeted antisense approaches have demonstrated the physiological importance of malate metabolism in the activation state of ADP-glucose pyrophosphorylase (AGPase), which is correlated with the accumulation of transitory starch and soluble solids at harvest (Centeno et al., 2011). However, due to the limited amount of information available on the connection between other organic acids metabolism and fruit quality, we cannot rule out a similar role for them during fruit development.

For certain fruits, citrate can be found in considerable concentrations. It is present from 8 to 15% (dry weight basis) in fruits such as strawberries and lemons (Citrus lemon). In both lemon and lime (Citrus aurantifolia) citrate accumulation can be as high as 8% of the fruit dry weight (Müller et al., 1996). The process involved in the metabolism and accumulation of citrate in mesocarp cells of fruits is under both genetic and environmental control. Several studies using different approaches as transcriptomics (Christelle et al., 2002), proteomics (Katz et al., 2011; Molassiotis et al., 2013) and metabolomics (Guo et al., 2016) have aided in the understanding of the different mechanisms involved in the control of the acidity and the quality of fruits. In addition, different agricultural practices including irrigation, nutrition (Kumar and Kumar, 2007) as well as controlled temperature (Burdon et al., 2007) can also impact the levels of fruit metabolites and as such the ratio between sweetness and acidity. However, there are no clear explanations for the changes observed in both malate and citrate in the cell.

To better understand how citrate metabolism is affected in Ponkan fruits, plants grown at low temperature and water stress in an open field experiment were compared to plants grown in optimal greenhouse conditions (Lin et al., 2016). It was observed that the expression levels of phosphoenolpyruvate carboxylase (PEPC), CS, ACO, and GAD were increased in response to low temperature, but not in water stressed plants compared to control conditions. These results, coupled with the changes in citrate levels under such conditions, indicated that low temperature may be a major factor influencing citrate metabolism during maturation in ponkan fruits. Similarly, it was observed that in sweet orange (Citrus sinensis), a non-climacteric fruit, the activities of the enzymes involved in organic acid metabolism including malic enzyme (ME), ICDH, ACO, and alcohol dehydrogenase increased during the first 3 weeks of post-harvest storage. Concomitantly, increased activity of enzymes involved in sugar catabolism such as hexokinase (HXK), Susy, UDPG pyrophosphorylase and PPi-dependent phosphofructokinase was also observed (Echeverria and Valich, 1989). Notably, these enzymes are necessary for organic acid usage and the subsequent oxidization of sugars in harvested sweet oranges (Echeverria and Valich, 1989). Pineapple is characterized by high contents of organic acids (Tables 1, 2), primarily controlled by the activity of key enzymes such as CS, ACO, PEPC, MDH, and ME. In particular, ACO seems to play a major role in modifying the acidity in pineapple (Saradhuldhat and Paull, 2007). Altogether, it seems reasonable to assume that a very tight connection between sugar and organic acid metabolism occurs during fruit development. However, exactly how this metabolic regulation occurs still remains to be elucidated.

Studies with papaya (Carica papaya), a typical climacteric fruit, have revealed that the accumulation of sugar, especially sucrose, occurs between 20 and 30 days before physiological maturation. During this stage, there is a significant increase in acid invertase (AI) activity with lower SPS and Susy activities in papaya mesocarp (Zhou and Paull, 2001). It has been also demonstrated that after harvesting there was still sucrose synthesis, and more importantly that the SPS activity is highly correlated with the sucrose content, indicating the importance of this enzyme during the ripening in papaya (Gomez et al., 2002). Although in papaya fruits the main organic acids are citrate, malate, and ascorbate, their accumulation occurs to relatively low concentrations (de Oliveira and Vitória, 2011). Particularly, citrate and malate contents are reduced over the course of ripening (for details see Table 2) (Brekke et al., 1971; Souza et al., 2014; Silva et al., 2015).

Analysis of sugars and organic acids content during the development of peach (Prunus persica) fruits showed that malate, quinate and shikimate concentrations were high at the beginning but declined at the end of fruit development (Wu et al., 2005). Thus, citrate concentration was maximal in immature fruits, whereas increased sugars concentration, mainly sucrose, occurred in mature fruits. Interestingly, during peach ripening, sucrose degradation was accompanied by an increase of glucose and fructose levels coupled with distinct regulation of transcripts encoding neutral invertases (NI), indicating differential or non-redundant functions of each putative NI isoform in peach (Borsani et al., 2009). Enzymes such as NI and PEPC were identified as important components of the carbon metabolism operating during peach post-harvest ripening (Borsani et al., 2009).

Malate is the predominant organic acid in many fruits, including both climacteric and non-climacteric fruits such as plum (Prunus salicina), banana, tomato, grape and apple (Morvai and Molnár-Perl, 1992; Sweetman et al., 2009; Centeno et al., 2011). Citrate is the predominant organic acid in citric fruits like oranges, lime and lemon (Albertini et al., 2006). Notably, citrate is also found as the main organic acid in grape, guava, papaya, pineapple and strawberry as show in Table 1 (Clements, 1964; Brekke et al., 1971; Jain et al., 2003; Batista Silva et al., 2018). Nevertheless, the accumulation and degradation of organic acids are not directly associated with respiratory and climacteric characteristics of the fruit. Thus, it is known that some climacteric fruits such as tomato appear to utilize malate during the respiratory burst (Goodenough et al., 1985). By contrast, banana and mango (Mangifera indica) continue to accumulate malate throughout ripening, even at the climacteric stage (Selvaraj and Kumar, 1989), whilst non-climacteric fruits also display widely varying malate accumulation and degradation (Sweetman et al., 2009). In addition, the accumulation of malate and citrate is seemingly a result of close interaction between metabolism and vacuolar storage and is also controlled by several environmental factors that affect the acidity of fleshy fruit by acting on various cellular mechanisms (Etienne et al. (2013). Taken together, the close relationship between organic acids and sugars metabolism during ripening seems to be a broadly connected factor that contribute in every way to the improvement of quality and flavor during fruit ripening. For this reason, it seems clear that a more in-depth understanding of the assessment of sugars and organic acids content and the use of genetic and agricultural tools capable of changing this relationship is of pivotal interest to food experts and researchers. Collectively, these results indicate that alterations in genes involved in the organic acids metabolism can determine the quality and extension of shelf-life of non-climacteric fruits, which have their physiological changes reduced after being detached from the plant.

Although hormones have been extensively studied as signaling molecules involved in different aspects of plant life cycle, it has been only recently that research has focused on understanding of their action during fruit development as well as in controlling sugars and organic acids metabolism in fruits during the ripening process (Figure 2) (McAtee et al., 2013; Karlova et al., 2014; Kumar et al., 2014). Accordingly, it has been demonstrated that hormones affect sugars and starch metabolism and that they can extend post-harvest life (Sagar et al., 2013a; Bastías et al., 2014; Karlova et al., 2014). However, there is a scarce literature available on the hormonal control of starch hydrolysis and the resulting sugar accumulation coupled with mitochondrial respiration (McAtee et al., 2013; Kumar et al., 2014). This fact apart, both the maturation and ripening have been associated in a number of studies to metabolic alterations involved with multiple genetic and biochemical pathways (Osorio et al., 2013). Although these changes have been observed in the context of responses to hormones (e.g., ethylene and ABA), the link between hormonal control and metabolite accumulation remains rather limited (Giovannoni, 2004; McAtee et al., 2013; Giovannoni et al., 2017).

The advent of ‘omics’ approaches has enabled significant progress in the characterization of hormone responses in fruits in general (Osorio et al., 2011). In addition, one important aspect of fruit development is the modulation of its metabolism, mainly driven by changes in sugars, organic acids and secondary metabolites immediately after fruit setting and partially recovering during or after ripening (Carrari et al., 2006). According to (Bapat et al., 2010), in climacteric fruit such as tomatoes, papaya, peaches, banana, apples, melon and other, ethylene synthesis plays a predominant role during ripening, and this still remains as one of the most studied hormones (Figure 2A). On the other hand, in non-climacteric fruits the respiratory burst and rise in ethylene production are not evident. It is widely accepted that although no single ‘master controller’ is able to control the ripening in non-climacteric fruits. Increased levels of different hormones like ethylene, abscisic acid (ABA), and brassinosteroids (BRs) have been suggested to promote ripening through complex interactions, whereas auxin delays some ripening associated process in those fruits (Figure 2B) (Fortes et al., 2015). Thus, we will now briefly discuss how changes in the main hormones involved in the process of formation and ripening of fruits impact organic acid metabolism, controlling fruit composition via crosstalk with other hormones or by themselves.

Ethylene has been shown to control many ripening-associated metabolic pathways. It is involved not only in the expression of senescence associated genes and defense signaling, but also in fruit ripening, where the autocatalytic ethylene production leads to changes in cell wall metabolism, carotenoid accumulation, chlorophyll degradation, synthesis of volatiles compounds, and modulation of sugars and acids contents (Giovannoni, 2001; Alexander and Grierson, 2002; Osorio et al., 2013; Farcuh et al., 2018).

The importance of ethylene in the production of aroma volatiles has been also genetically demonstrated by the antisense suppression of ethylene production, which resulted in strong inhibition of aroma in melon (Cucumis melo L.) fruits (Ayub et al., 1996). The ripening of the climacteric fruit peach is largely controlled by ethylene and thus increase ethylene production leads to enhanced respiration coupled with changes in both chemical composition and physical characteristics of the fruit (Paul et al., 2012). Furthermore, enhanced ethylene biosynthesis are accompanied by increased levels of citrate, malate and glucose and fructose but decreased sorbitol and sucrose levels following harvesting (Borsani et al., 2009).

It has been also shown that ethylene is involved in an organ-specific manner in strawberry fruit ripening by differentially controlling the levels of amino acids, glucose, and fructose, as well as citrate and malate in the achene and the receptacle (Merchante et al., 2013). Strawberry plants with altered sensitivity to ethylene were used to unravel its role during fruit ripening process, as well as to further enhance our understanding of the modulation of metabolic pathways (Merchante et al., 2013). Similarly, it has been demonstrated that in grape, a non-climacteric fruit, ethylene seems to be also required for berry development and ripening (Chervin et al., 2004). Indeed, it has been suggested that ethylene could be triggering the onset of ripening. In fact, Ethylene Responsive Factor (VviERF045) from grape affects a range of different processes including, photosynthetic capacity, secondary metabolism, expression of key genes related to changes in epidermis and cuticle of the berry, cell expansion, as well as activation of several defense related genes (Leida et al., 2016).

Recent examples of cross-talk among different hormones have revealed a highly complex interplay of signals during grape development and ripening (Fortes et al., 2015). Accordingly, in non-climacteric fruits the responses of ethylene seem to be associated, via highly specific cross-talk, with other hormones such as ABA, auxin (Davies et al., 1997; McAtee et al., 2013) and BRs (Symons et al., 2006), all of which are known to play a functional role in grape berry ripening. Non-climacteric fruits may also display climacteric-like behavior following harvest (Katz et al., 2004). Similarly, differential expression of component of the ethylene-signaling pathway have been also observed in several non-climacteric fruits including citrus and grape (Tesniere et al., 2004; Trainotti et al., 2005).

The participation of ethylene in ripening has been extensively investigated in tomato fruits using several mutant that drastically affect the ripening processes of tomatoes fruits. For instance, ripening inhibitor (rin), non-ripening (nor), green ripe (Gr), green-flesh (gf), colorless non-ripening (Cnr), never ripe (Nr), high pigment 1 (hp1), high pigment 2 (hp2), and dark green (dg) have been investigated in the context of ripening (Lanahan et al., 1994; Mustilli et al., 1999; Vrebalov et al., 2002; Levin et al., 2003).

Although the use of such mutants has clearly provided significant insights on the respective functional roles and also hierarchical regulation based on each gene (Giovannoni, 2004), the complete understanding of the ripening regulatory network remains rather fragmented. Nevertheless, by analyzing three dominant ripening mutants of tomato, nor, rin, and Nr, along the developmental and ripening periods it was possible to identify very strong correlations between ripening-associated transcripts and specific metabolite groups, such as organic acids from the TCA cycle, sugars, and cell wall-related metabolites, such as lipoxygenase, pectate lyase and poligalacturonase (PG) underlining the importance of these metabolic pathways during fruit ripening (Carrari et al., 2006; Centeno et al., 2011; Osorio et al., 2011). Organic acids, including the two TCA cycle intermediates malate and citrate, were strongly affected across ripening, suggesting that organic acids are regulated at the transcriptional level in climacteric fruit. Importantly, malate plays a crucial role in transitory starch metabolism in normal tomato fruit development and ripening and it seems that its regulation is also conserved in non-climacteric fruits (Centeno et al., 2011; Osorio et al., 2011, 2012, 2013). Additionally, in strawberry fruit organic acids including succinate, fumarate and 2-oxoglutarate displayed substantial changes during ripening, associated with a heavy demand for carbon skeleton components (Fait et al., 2008). In pepper fruit, citrate, dehydroascorbate, and malate are highly correlated to genes associated with starch and cell wall pathways as well as protein degradation, suggesting the importance of these organic acids during pepper fruit development and ripening (Osorio et al., 2012). Altogether, these results underlie the pivotal significance of the metabolic pathways associated with sugars and organic acids, revealing also multiple ethylene-associated events that occurs during climacteric and non-climacteric fruit ripening. It is important to mention that ethylene does not act regulating ripening alone but it rather works likely in conjunction with others phytohormones such as auxin, ABA, and cytokinin (McAtee et al., 2013; Kumar et al., 2014).

Future studies should therefore explore the hormone signaling network by combining model plant based knowledge on the molecular mechanisms involved in hormone signaling and the association with available genome information of other plant species. In apple fruit, the main organic acid is malate (Table 1). By using the 1-methylcyclopropene (1-MCP) (inhibitor of ethylene perception) it has recently been shown that ethylene is involved in the regulation of the levels of organic acid once this compound delayed the reduction of malate and citrate content during ripening (Lu et al., 2013).

In fruits with lower ethylene requirement to ripen, ABA appears to have a crucial role given its increase following ripening process (Setha, 2012). In strawberry, a non-climacteric fruit model, the effect of ABA has been investigated (Jiang and Joyce, 2003) demonstrating that endogenous ABA may play a role in changes of fruit color during ripening via an up-regulation of both ethylene production and phenylalanine ammonia-lyase (PAL) activity. In good agreement, compelling evidence suggest that exogenous ABA can significantly accelerate strawberry fruit ripening, most likely by the down regulation of 9-cis-epoxycarotenoid dioxygenase gene (FaNCED1) as demonstrated by virus-induced gene silencing (VIGS) leading to decreased content of ABA that can significantly retard the ripening (Jia et al., 2011). The FaNCED1 is a predominant contributor to ABA accumulation during fruit ripening and it has been also evidenced that soluble sugars, especially sucrose, may act as a promoter to trigger ABA accumulation (Jia et al., 2011). The interaction between sugar and ABA has been recently reviewed by (Li et al., 2011), suggesting a core mechanism involved in the regulation of non-climacteric fruit ripening. Remarkable, reduced expression of NCED in strawberry resulted in delayed fruit maturation with changes in several metabolites such as organic acids and sugars implicating ABA in the control of fruit quality.

In climacteric fruits such as tomato and banana the levels of ABA increased before an increase in ethylene (McAtee et al., 2013). Remarkably, ABA signaling may also impact different aspects of fruit maturation (Sun et al., 2012). Exogenous ABA treatment consequently increase the ABA content in both flesh fruits and seeds, triggering ethylene biosynthesis by the up regulation of ACS and ACO expression and therefore inducing fruit ripening (Zhang et al., 2009). It has been also suggested that LeNCED1, which initiates ABA biosynthesis at the onset of fruit ripening, can be the original inductor of ABA accumulation and might play a key role not only in the ripening process but also during the senescence of tomato fruits (Zhang et al., 2009). The suppression of the gene encoding NCED1 resulted in a down regulation of several other genes involved in ripening process including the cell wall related PG and pectinmethylesterase (PME), which can also contribute to changes in TCA cycle intermediates (Sun et al., 2012). Although those studies collectively provided evidence that ABA is involved in fruit maturation, it still remains unclear whether ABA acts directly or via altering ethylene levels, given the already well established cross-talk between those hormones.

Overexpression of ABA-responsive elements SlAREB1 in tomato, resulted in increased content of organic acids (e.g., citrate and malate), hexoses, hexose-phosphates, and amino acids in immature green, mature green, and red ripe fruits (Bastías et al., 2014). These modifications correlated with an up-regulation of genes encoding enzymes involved in carbohydrate and amino acid metabolism suggesting a possible role for this transcription factor in the regulation of fruit organoleptic properties (Bastías et al., 2014). Whether modification of the expression of other enzymes of the TCA cycle involved in the synthesis of organic acids and amino acids are affected by SlAREB1 remains to be determined. In tomato fruits, organic acids are a crucial quality determinant during ripening process and flavor, and correlate with the expression of genes associated with ethylene and cell wall metabolism-related pathways (Carrari et al., 2006; Carrari and Fernie, 2006; Osorio et al., 2012). Further studies are clearly required to elucidate the real mechanism connecting ABA and fruit ripening as well as metabolites changes and fruit quality.

It is currently accepted that auxin participates in various processes ranging from fruit formation to ripening, mainly via a crosstalk between gibberellins and ethylene (McAtee et al., 2013). In fact, auxin coordinates the ethylene synthesis consequently the ripening process (Li et al., 2016). Accordingly, genes related to carotenoid metabolism, cell degradation, and energy metabolism were strongly down-regulated by exogenous auxin further impacting tomato ripening (Su et al., 2015). Recently, RNA-Seq analysis of tomato fruit following exogenous auxin application has shown that several genes involved in the TCA cycle and oxidative phosphorylation pathway were significantly down-regulated indicating that auxin affects fruit ripening by impacting mainly fruit respiration rate (Li et al., 2016). Moreover, auxin-treated fruits were characterized by increased levels of citrate, succinate and malate which indicate that auxin application seems to enhance fruit acidity (Li et al., 2017). Furthermore, exogenous auxin altered the expression patterns of ethylene and auxin signaling-related genes during ripening, suggesting a significant crosstalk between these two hormones during tomato ripening (Li et al., 2016). Recently, an important role for auxin during ripening as a modulator of the levels of sugar and organic acids has been demonstrated in tomato fruits (Sagar et al., 2013a; Hao et al., 2016; Li et al., 2017).

Recent studies have also demonstrated that loss or gain of function of several auxin response genes, such as SlARF4, SlARF2a, SlIAA17 and SlIAA27, leads to conspicuous changes in fruit pigment accumulation, sugar content, starch accumulation, phenylpropanoids component, organic acids contents and other fruit quality attributes (Bassa et al., 2013; Sagar et al., 2013a,b; Hao et al., 2015; Su et al., 2015). By using a transcriptome analysis approach Li et al. (2016) have suggested that exogenous auxin retards tomato ripening process and interferes on the normal expression patterns of many genes involved in metabolic pathways. More recently, Li et al. (2017) analyzed the metabolic changes following exogenous auxin showing that besides metabolites such as sugars and amino acids, a total of nine organic acids were detected in tomato fruits under different developmental stages. Briefly, higher contents of succinate and ascorbate when compared with control samples were observed 10 days after auxin treatment. Notably, auxin seems to affect citrate levels keeping it higher than in control fruits at the end of ripening, indicating that auxin application might increase fruit acidity, affecting sour taste of fruit (Li et al., 2017).

Over the last decades have witnessed the characterization of numerous mutants for synthesis or signaling of several hormones in different model species such as Arabidopsis (Gazzarrini and McCourt, 2003), tomato (Carvalho et al., 2011), and rice (Yang D.-L. et al., 2013). This resource, coupled with the integration of transcriptomics and metabolomics approaches, has greatly enhanced our understanding of the molecular and biochemical events associated with ripening in both climacteric and non-climacteric fruits. However, despite our current understanding of how organic acid metabolism is associated with hormones metabolism, the exact mechanisms underlying their interaction during fruit ripening clearly require further elucidation.

The role of GA is well established during fruit-set and fruit development, controlling the cell expansion and it has been revisited recently (McAtee et al., 2013; Obroucheva, 2014). However, there is evidence that GA can delay tomato fruit ripening by preventing some of the changes triggered by ethylene. Unfortunately, relatively little work is current available directly connecting gibberellins and metabolic changes in fruits. Nevertheless, some advances were observed on this theme. Accordingly, the impacts of GAs on primary metabolism have been also previously demonstrated in tomato plants with reduced levels of the TCA cycle enzyme 2-OGDH (Araújo et al., 2014a). In the same vein, it has been observed that gibberellic acid (GA3) causes ripening delay in citrus (Biale, 1978) and mango fruits, reducing the ascorbate content (Kader, 2008). In strawberry, GA3 showed an inhibitory effect on fruit ripening, evidenced by a decrease in the respiratory activity (Martínez et al., 1994). GAs seems to affect the primary metabolism mediated by changes in 2-oxoglutarate, thus linking TCA cycle function with amino acid, glucosinolate, flavonoid, alkaloid, and gibberellin biosynthesis (Araújo et al., 2014a). Defining the precise nature of the interaction between organic acids coupled with the GA-mediated regulation of fruit clearly remains an exciting topic for future research.

Due to the multifunctionality of BRs, more attention has been given to their association with fruit ripening recently. BRs plays an important regulatory role in various physiological processes, including growth, seed germination, flowering, changes in enzymatic activities, and fruit set (Clouse and Sasse, 1998; Khripach et al., 1998; Sánchez-Rodríguez et al., 2017) and has been recently associated with fruit ripening. Exogenous BRs analogs on endive (Cichorium endivia L.) play an important role in increasing the contents of the organic acids such as citrate, oxaloacetate and succinate (Mario et al., 2013). Mazorra Morales et al. (2014) showed the interconnection between BRs and ethylene in the regulation of the mitochondrial electron transport chain in post-harvest of papaya fruits. The authors showed that exogenous BRs application affect the AOX-dependent electron transport, which is antagonized by ethylene, suggesting that, BRs and ethylene act antagonistically regulating the AOX capacity during papaya ripening. The role of BR application has been also investigated in strawberry, suggesting it as an important molecule to improve qualities traits, mainly by increasing soluble solid contents, inducing sugar and organic acids content, as well as the production of secondary metabolites such as anthocyanin and phenolic compounds (Rafeii, 2017). The role of BRs during fruit ripening has been also investigated in various fruits such as tomato (Vidya Vardhini and Rao, 2002), grapes (Symons et al., 2006), papaya (Mazorra et al., 2013), strawberry (Mohammadrezakhani et al., 2016), and mango (Zaharah et al., 2012). Notably, it is directly related with an extensive crosstalk with ethylene levels, affecting numerous processes. However, relatively few studies have clearly demonstrated the impacts of this phytohormone on primary metabolism and specifically at the organic acids, although it is possible to observe that their content usually increase in presence of exogenous BRs, which can be an interesting avenue for research.

Polyamines (PAs), another group of signaling molecules, has been extensively studied in recent years. PAs are small aliphatic amines with an important role in plant growth process including fruit ripening and (Walden et al., 1997; Guo et al., 2018; Wuddineh et al., 2018). In plants, PAs are initially converted from glutamate, a key amino acid involved in N assimilation, to putrescine (Put), then converted to spermidine (Spd) and, in the end, to spermine (Spm) by the action of Spd synthase (SPDS) and Spm synthase (SPMS) being further decarboxylated to S-adenosyl-L-methionine (dcSAM) generating SAM as a reaction product which is catalyzed by SAM decarboxylase (SAMDC) (Wen-Wei et al., 2006; Michael, 2016; Guo et al., 2018). SAM is a common precursor for both PA and ethylene biosynthesis but their physiological functions are distinct at times and can be antagonist mainly during senescence (Pandey et al., 2000).

Accordingly, Gupta et al. (2013) showed that silencing of 1-aminopropane-1-carboxylate synthase gene (SlACS) delays ripening simultaneously improving fruit quality in tomato and increasing the PAs levels associated with down-regulation of cell wall hydrolyses. Notably, still in tomato fruit, PAs has been identified as a great contributor of fruit ripening mainly associated with the activity of both ornithine decarboxylase (ODC) and arginine decarboxylase (ADC) (Rastogi and Davies, 1990, 1991). In this vein, Pandey et al. (2015) demonstrated that the overexpression of ODC triggers the biosynthesis of Put, Spd and SPM which, in its turn, inhibits ethylene production delaying fruit ripening, but enhances tomato fruit quality traits. Additionally, overexpression of SPDS in tomato promote fruit ripening, increasing sugars content, as well as lycopene coupled with ethylene production (Neily et al., 2011). In grape fruits, PAs also have an important role in the aroma development (Fortes et al., 2015), while in peach it plays a key role in fruit firmness and soluble sugar content followed by an abrupt decreased in Put during post-harvest (Liu et al., 2006). Application of exogenous Spr in peach fruits reduced ripening by impacting ethylene and auxin metabolism and signaling (Patrizia et al., 2012). Remarkably, polyamines are reported to be important molecules involved in strawberry ripening (Tilak and Raymond, 1996). Recently, demonstrated that PAs, especially spermine (Spm), regulate strawberry fruit ripening in an ABA-dominated, IAA-participating and ethylene-coordinated manner controlling several physiological parameters, including firmness, and the content of anthocyanin, sugar, polyamine, auxin (IAA), abscisic acid (ABA), as well as ethylene emission. Notably, these changes are coupled with alterations in FaSAMDC expression which can promote and inhibit ripening (Guo et al., 2018). PAs play also important functions in several others fruits in a manner which may generate controversial conclusions, thus it is important to mention that, more studies are required to further understand the significance and roles of PAs in dry and fleshy fruit development.

Lastly, but not least important, very few studies have demonstrated the association between salicylic acid (SA) and the maintenance of fruit quality during post-harvest. Sweet cherry treated with exogenous SA revealed an effective and environmentally friendly tool to maintain fruit quality during storage associated with the maintenance of the sugar and organic acid content in the fruit as well as with enhancements of both the concentration of bioactive compounds concentration and the antioxidant activity (Giménez et al., 2016). Interestingly, SA also culminated with delays on ripening process in banana (Srivastava and Dwivedi, 2000), sweet cherry (Yao and Tian, 2005), and kiwifruit. In all the above mentioned results, SA seems to act inhibiting fruit ripening, mainly by reducing not only the respiratory rate but also sugar and total acid content. It seems reasonable to assume that coupling the application of such hormones or chemical compounds with both molecular and metabolic analysis in order to provide information concerning the role of hormones in the regulation of fruit taste should greatly facilitate advances in our understanding of the metabolic control mediated by hormones in fruits.