Molinie, Thibaut; Cougouilles, Elodie; David, Claudine; Cahoreau, Edern; Portais, Jean-Charles; Mourier, Arnaud published the artcile< MDH2 produced OAA is a metabolic switch rewiring the fuelling of respiratory chain and TCA cycle>, Electric Literature of 112-63-0, the main research area is mitochondrial respiratory chain MDH2 oxaloacetate TCA cycle; Bioenergetics; MDH2; Malate aspartate shuttle; Mitochondria; NADH redox homeostasis; Oxaloacetate; Respirasomes; Respiratory chain supercomplexes.
The mitochondrial respiratory chain (RC) enables many metabolic processes by regenerating both mitochondrial and cytosolic NAD+ and ATP. The oxidation by the RC of the NADH metabolically produced in the cytosol involves redox shuttles as the malate-aspartate shuttle (MAS) and is of paramount importance for cell fate. However, the specific metabolic regulations allowing mitochondrial respiration to prioritize NADH oxidation in response to high NADH/NAD+ redox stress have not been elucidated. The recent discovery that complex I (NADH dehydrogenase), and not complex II (Succinate dehydrogenase), can assemble with other respiratory chain complexes to form functional entities called respirasomes, led to the assumption that this supramol. organization would favor NADH oxidation Unexpectedly, characterization of heart and liver mitochondria demonstrates that the RC systematically favors electrons provided by the respirasome free complex II. Our results demonstrate that the preferential succinate driven respiration is tightly controlled by OAA levels, and that OAA feedback inhibition of complex II rewires RC fuelling increasing NADH oxidation capacity. This new regulatory mechanism synergistically increases RCs NADH oxidative capacity and rewires MDH2 driven anaplerosis of the TCA, preventing malate production from succinate to favor oxidation of cytosolic malate. This regulatory mechanism synergistically adjusts RC and TCA fuelling in response to extramitochondrial malate produced by the MAS.
Biochimica et Biophysica Acta, Bioenergetics published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (UQCR2). 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Electric Literature of 112-63-0.
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