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Mitochondrial Proteomics: Understanding Mitochondria Function and Dysfunction Through the Characterization of Their Proteome

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Mitochondria are undoubtedly the powerhouse of eukaryotic cells. Through the oxidative phosphorylation machinery (OXOPHOS) they synthesize ATP for the energy metabolism, moreover, they are involved in a plethora of cellular mechanisms such as metabolic pathways, stress response, cell signalling and apoptosis. ...

Mitochondria are undoubtedly the powerhouse of eukaryotic cells. Through the oxidative phosphorylation machinery (OXOPHOS) they synthesize ATP for the energy metabolism, moreover, they are involved in a plethora of cellular mechanisms such as metabolic pathways, stress response, cell signalling and apoptosis. Indeed, their complex role makes the mitochondria very important organelles in the life cycle of eukaryotic organisms, with their dysfunction being strictly associated with a series of pathological conditions.


According to the endosymbiosis theory, diverse eukaryotic cell organelles (among which are the mitochondria) derive from bacteria, since they structurally and functionally resemble an autonomous organism. However, the mitochondrial genome encodes only a small subset of proteins (14 proteins), which are mostly membrane proteins located at the Inner Mitochondrial Membrane and are involved in the OXPHOS energy-producing machinery. The majority of proteins defining mitochondrial structure and function are encoded by nuclear genes. This leads to high phenotypic plasticity, which is a fundamental molecular basis for the different roles that mitochondria play in different cellular and tissue compartments. This adaptive capacity has been only initially addressed, and a new generation of OMICS investigations would be needed to provide the key evidence of such a functional rearrangement.


In the last 20 years, proteomics studies, mostly based on Mass Spectrometry protein detections, have allowed the identification of thousands of proteins associated with mitochondria and have led to the increased comprehension of mitochondrial function in physiological and pathophysiological conditions. Moreover, with the help of bioinformatic tools and systems biology studies, the interaction between the mitochondria and other cell compartments became more evident and led to the implementation of studies devoted to unraveling mitochondrial importance in the delicate balance of life. Last, but not least, within the frame of the Human Proteome Project initiative (HPP) started from Human Proteome Organization (HUPO) community in 2010, the challenging scientific aim to map the entire human proteome in a systematic and coordinated international effort using currently available and emerging techniques was defined. Two complementary projects were launched: the Chromosome-Centric Human Proteome Project (C-HPP) and the Biology/Disease-driven-Human Proteome Project (B/D-HPP), that proceed in a constant and mutual interaction under the support of the HUPO resource pillars for mass spectrometry (MS), antibody profiling (Ab), and public knowledge bases of genomics, transcriptomics and proteomics.


The aim of this Research Topic on Mitochondrial Proteomics is to gain more information about mitochondrial structure and function in order to unveil unknown aspects, or to clarify complex mechanisms, of:
- mitochondrial physiological function (e.g. cell life and death signalling, energy production and cellular redox balance)
- mitochondrial dysfunction in metabolic and neurodegenerative diseases (e.g. Diabetes, ASL, PD, AD).


In this Research Topic, we welcome Reviews, Mini Reviews, Commentaries, Methods and Original Research papers which discuss the use of OMICS data, with particular focus on Proteomics ( e.g. discovery, quantitative, PTMs and redox proteomics), both independently or in combination with more classical biochemical, molecular and cellular approaches. This will hopefully provide deeper insight into the physiological or pathophysiological mechanisms involving the mitochondria and will potentially shed light on new roles for these incredible organelles.


Keywords: Mitochondria, Proteome, Post-translational Modifications, Metabolism, Neurodegeneration


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