About this Research Topic
One of the outstanding problems in cell energy metabolism concerns the role of mitochondria. In addition to their role as cell powerhouse, with ATP synthesis occurring in the oxidative phosphorylation, these organelles play a crucial role in certain pathways including gluconeogenesis, fatty acid synthesis and oxidation, aminoacid metabolism, urea cycle etc. In addition, mitochondria play a role in glycolysis as can be deduced from the occurrence of mitochondrial shuttles and the recent discovery that both L-lactate and D-lactate dehydrogenases and pyruvate kinase are present in them. These findings give rise to the question of how the traffic of metabolites and other compounds across the mitochondrial membrane occurs and what role this transport plays in regulating certain metabolic pathways both under physiological and pathological conditions. A search for “mitochondrial transport and metabolism” in brain, liver, heart, kidney, muscle, lung, cancer cells, lymphocytes and erythrocytes in PubMed, WEB of sciences and Scopus shows that only 8-16% refer to brain mitochondria. Given that a variety of neurological diseases depends on the impairment of the mitochondria function, further research is needed; indeed, due to the heterogeneity of cell structures and functions, conclusions obtained from experimental work carried out with certain isolated mitochondria cannot be directly applied to other cellular or whole tissue systems.
Accordingly, use of the reconstituted systems may provide only some indications, but not final conclusions regarding mitochondrial transport since it requires a variety of a priori assumptions about (1) the interactions between transport proteins and the liposomal membrane and whether or not they mirror the mitochondrial membrane environment; (2) the protein/substrate interaction and its similarity to that of the isolated mitochondria; (3) the proteoliposome internal volume and whether or not it mirrors the matrix space; (4) the similarity in the energy that drives the process in mitochondria and in the reconstituted system and the assumption that other mitochondrial components have no significant effects on this transport.
This Research Topic aims to provide new insights into important issues concerning brain mitochondria. Among these are methodologies for isolation of coupled mitochondria both from brain and from selected area of it, mitochondrial transport of glucose and lipid metabolites and characterization of mitochondrial carriers under pathophysiological conditions, such as the ADP/ATP carrier, the dicarboxylate and tricarboxylate carriers, the fumarate, the phosphate carriers, the aspartate/glutamate carrier, the L- and D-lactate carriers, the pyruvate carrier, the amino acid carriers, the uncoupling protein, the aquaporin etc. Due to the increasing interest of genomic defects which result in impairment of the oxidative phosphorylation in mitochondrial diseases and given that oxidative phosphorylation mostly depends on the mitochondrial metabolite traffic across the mitochondrial membrane, the perspectives on the role of mitochondrial transport in the metabolic pathways leading to disease merit some consideration. Finally, the elucidation of the mitochondrial mechanisms by which neurological diseases takes place as well as the development of pharmacological therapy in which mitochondria are targets is an important issue to be pursued.
Keywords: Mitochondria, Metabolite Transport, Energy Metabolism, Brain, Brain Pathology
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