The mitochondrial mRNA stabilizing protein, SLIRP, regulates skeletal muscle mitochondrial structure and respiration by exercise-recoverable mechanisms-Reference-Cited by-同舟云学术

The mitochondrial mRNA stabilizing protein, SLIRP, regulates skeletal muscle mitochondrial structure and respiration by exercise-recoverable mechanisms

Published:2023-10-30 Issue: Volume: Page:
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Pham Tang Cam Phung^ORCID,Raun Steffen Henning^ORCID,Havula Essi^ORCID,Henriquez-Olguín Carlos^ORCID,Rubalcava-Gracia Diana^ORCID,Frank Emma^ORCID,Fritzen Andreas Mæchel^ORCID,Jannig Paulo R.^ORCID,Andersen Nicoline Resen^ORCID,Kruse Rikke^ORCID,Ali Mona Sadek^ORCID,Halling Jens Frey^ORCID,Ringholm Stine^ORCID,Needham Elise J.^ORCID,Hansen Solvejg^ORCID,Lemminger Anders Krogh^ORCID,Schjerling Peter^ORCID,Petersen Maria Houborg^ORCID,de Almeida Martin Eisemann^ORCID,Jensen Thomas Elbenhardt^ORCID,Kiens Bente^ORCID,Hostrup Morten^ORCID,Larsen Steen^ORCID,Ørtenblad Niels^ORCID,Højlund Kurt^ORCID,Kjær Michael^ORCID,Ruas Jorge L.^ORCID,Trifunovic Aleksandra^ORCID,Wojtaszewski Jørgen Frank Pind^ORCID,Nielsen Joachim^ORCID,Qvortrup Klaus^ORCID,Pilegaard Henriette^ORCID,Richter Erik Arne^ORCID,Sylow Lykke^ORCID

Abstract

Summary and graphical abstractDecline in mitochondrial function associates with decreased muscle mass and strength in multiple conditions, including sarcopenia and type 2 diabetes. Optimal treatment could include improving mitochondrial function, however, there are limited and equivocal data regarding the molecular cues controlling muscle mitochondrial plasticity. Here we uncover the mitochondrial-mRNA-stabilizing protein SLIRP, in complex with LRPPRC, as a PGC-1α target that regulates mitochondrial structure, respiration, and mitochondrially-encoded-mRNA pools in skeletal muscle. Exercise training effectively counteracted mitochondrial defects induced by loss of LRPPRC/SLIRP, despite sustained low mitochondrially-encoded-mRNA pools, via increased mitoribosome translation capacity. In humans, exercise training robustly increased muscle SLIRP and LRPPRC protein content across exercise modalities and sexes, yet this increase was less prominent in subjects with type 2 diabetes. Our work identifies a mechanism of post-transcriptional mitochondrial regulation in skeletal muscle through mitochondrial mRNA stabilization. It emphasizes exercise as an effective approach to alleviate mitochondrial defects by possibly increasing mitoribosome capacity.Abstract Figure

Publisher

Cold Spring Harbor Laboratory

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