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Fernandez-Vizarra 2022 Cell Metab

From Bioblast
Publications in the MiPMap
Fernández-Vizarra E, López-Calcerrada S, Sierra-Magro A, Pérez-Pérez R, Formosa LE, Hock DH, Illescas M, Peñas A, Brischigliaro M, Ding S, Fearnley IM, Tzoulis C, Pitceathly RDS, Arenas J, Martín MA, Stroud DA, Zeviani M, Ryan MT, Ugalde C (2022) Two independent respiratory chains adapt OXPHOS performance to glycolytic switch.

» Cell Metab 34:1792-808.e6. PMID: 36198313

Fernandez-Vizarra Erika,  Lopez-Calcerrada Sandra,  Sierra-Magro Ana,  Perez-Perez Rafael,  Formosa Luke E,  Hock Daniella H,  Illescas Maria,  Penas Ana, Brischigliaro Michele,  Ding Shujing,  Fearnley Ian M,  Tzoulis Charalampos,  Pitceathly Robert DS,  Arenas Joaquin, Martin Miguel A,  Stroud David A,  Zeviani Massimo,  Ryan Michael T,  Ugalde Cristina (2022) Cell Metab

Abstract: The structural and functional organization of the mitochondrial respiratory chain (MRC) remains intensely debated. Here, we show the co-existence of two separate MRC organizations in human cells and postmitotic tissues, C-MRC and S-MRC, defined by the preferential expression of three COX7A subunit isoforms, COX7A1/2 and SCAFI (COX7A2L). COX7A isoforms promote the functional reorganization of distinct co-existing MRC structures to prevent metabolic exhaustion and MRC deficiency. Notably, prevalence of each MRC organization is reversibly regulated by the activation state of the pyruvate dehydrogenase complex (PDC). Under oxidative conditions, the C-MRC is bioenergetically more efficient, whereas the S-MRC preferentially maintains oxidative phosphorylation (OXPHOS) upon metabolic rewiring toward glycolysis. We show a link between the metabolic signatures converging at the PDC and the structural and functional organization of the MRC, challenging the widespread notion of the MRC as a single functional unit and concluding that its structural heterogeneity warrants optimal adaptation to metabolic function. Keywords: COX7A1–2, SCAFI/COX7RP/COX7A2L, Bioenergetics, Glycolysis, Metabolic switch, Mitochondria, Oxidative metabolism, Pyruvate dehydrogenase, Respiratory chain organizations, Respiratory supercomplexes Bioblast editor: Plangger M O2k-Network Lab: IT Padova Viscomi C

Labels: MiParea: Respiration, Genetic knockout;overexpression 

Organism: Human  Tissue;cell: HEK  Preparation: Permeabilized cells, Intact cells  Enzyme: Supercomplex 

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