Molinie 2022 Biochim Biophys Acta Bioenerg

From Bioblast
Jump to navigation Jump to search
Publications in the MiPMap
Molinié T, Cougouilles E, David C, Cahoreau E, Portais JC, Mourier A (2022) MDH2 produced OAA is a metabolic switch rewiring the fuelling of respiratory chain and TCA cycle. Biochim Biophys Acta Bioenerg 1863:148532.

» PMID: 35063410 Open Access

Molinie Thibaut, Cougouilles Elodie, David Claudine, Cahoreau Edern, Portais Jean-Charles, Mourier Arnaud (2022) Biochim Biophys Acta Bioenerg

Abstract: 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 supramolecular organization would favour NADH oxidation. Unexpectedly, characterization of heart and liver mitochondria demonstrates that the RC systematically favours 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 RC's NADH oxidative capacity and rewires MDH2 driven anaplerosis of the TCA, preventing malate production from succinate to favour oxidation of cytosolic malate. This regulatory mechanism synergistically adjusts RC and TCA fuelling in response to extramitochondrial malate produced by the MAS. Keywords: Bioenergetics, MDH2, Malate aspartate shuttle, Mitochondria, NADH redox homeostasis, Oxaloacetate, Respirasomes, Respiratory chain supercomplexes Bioblast editor: Plangger M O2k-Network Lab: FR Bordeaux Mourier A


Labels: MiParea: Respiration 


Organism: Mouse  Tissue;cell: Heart, Liver  Preparation: Isolated mitochondria 


Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k 

2022-03