Zanou 2021 Nat Commun

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Zanou N, Dridi H, Reiken S, Imamura de Lima T, Donnelly C, De Marchi U, Ferrini M, Vidal J, Sittenfeld L, Feige JN, Garcia-Roves PM, Lopez-Mejia IC, Marks AR, Auwerx J, Kayser B, Place N (2021) Acute RyR1 Ca2+ leak enhances NADH-linked mitochondrial respiratory capacity. Nat Commun 12:7219.

» PMID: 34893614 Open Access »O2k-brief

Zanou Nadege, Dridi Haikel, Reiken Steven, Imamura de Lima Tanes, Donnelly Chris, De Marchi Umberto, Ferrini Manuele, Vidal Jeremy, Sittenfeld Leah, Feige Jerome N, Garcia-Roves Pablo M, Lopez-Mejia Isabel C, Marks Andrew R, Auwerx Johan, Kayser Bengt, Place Nicolas (2021) Nat Commun

Abstract: Sustained ryanodine receptor (RyR) Ca2+ leak is associated with pathological conditions such as heart failure or skeletal muscle weakness. We report that a single session of sprint interval training (SIT), but not of moderate intensity continuous training (MICT), triggers RyR1 protein oxidation and nitrosylation leading to calstabin1 dissociation in healthy human muscle and in in vitro SIT models (simulated SIT or S-SIT). This is accompanied by decreased sarcoplasmic reticulum Ca2+ content, increased levels of mitochondrial oxidative phosphorylation proteins, supercomplex formation and enhanced NADH-linked mitochondrial respiratory capacity. Mechanistically, (S-)SIT increases mitochondrial Ca2+ uptake in mouse myotubes and muscle fibres, and decreases pyruvate dehydrogenase phosphorylation in human muscle and mouse myotubes. Countering Ca2+ leak or preventing mitochondrial Ca2+ uptake blunts S-SIT-induced adaptations, a result supported by proteomic analyses. Here we show that triggering acute transient Ca2+ leak through RyR1 in healthy muscle may contribute to the multiple health promoting benefits of exercise.

Bioblast editor: Plangger M O2k-Network Lab: CH Lausanne Place N, ES Barcelona Garcia-Roves PM


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style 


Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized cells 


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

2021-12, O2k-brief