Academic Journal
The mitochondrial mRNA-stabilizing protein SLIRP regulates skeletal muscle mitochondrial structure and respiration by exercise-recoverable mechanisms
| العنوان: | The mitochondrial mRNA-stabilizing protein SLIRP regulates skeletal muscle mitochondrial structure and respiration by exercise-recoverable mechanisms |
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| المؤلفون: | Pham, Tang Cam Phung, Raun, Steffen Henning, Havula, Essi, Henriquez-Olguín, Carlos, Rubalcava-Gracia, Diana, Frank, Emma, Fritzen, Andreas Mæchel, Jannig, Paulo R, Andersen, Nicoline Resen, Kruse, Rikke, Ali, Mona Sadek, Irazoki, Andrea, Halling, Jens Frey, Ringholm, Stine, Needham, Elise J, Hansen, Solvejg, Lemminger, Anders Krogh, Schjerling, Peter, Petersen, Maria Houborg, de Almeida, Martin Eisemann, Jensen, Thomas Elbenhardt, Kiens, Bente, Hostrup, Morten, Larsen, Steen, Ørtenblad, Niels, Højlund, Kurt, Kjær, Michael, Ruas, Jorge L, Trifunovic, Aleksandra, Wojtaszewski, Jørgen Frank Pind, Nielsen, Joachim, Qvortrup, Klaus, Pilegaard, Henriette, Richter, Erik Arne, Sylow, Lykke |
| المصدر: | Pham , T C P , Raun , S H , Havula , E , Henriquez-Olguín , C , Rubalcava-Gracia , D , Frank , E , Fritzen , A M , Jannig , P R , Andersen , N R , Kruse , R , Ali , M S , Irazoki , A , Halling , J F , Ringholm , S , Needham , E J , Hansen , S , Lemminger , A K , Schjerling , P , Petersen , M H , de Almeida , M E , Jensen , T E , Kiens .... |
| سنة النشر: | 2024 |
| المجموعة: | University of Southern Denmark: Research Output / Syddansk Universitet |
| مصطلحات موضوعية: | Animals, Humans, Muscle, Skeletal/metabolism, RNA-Binding Proteins/metabolism, Male, RNA, Messenger/metabolism, Female, Mitochondria, Muscle/metabolism, Physical Conditioning, Animal, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism, Mitochondrial Proteins/metabolism, DNA, Mitochondrial/genetics, Mice, Drosophila melanogaster/genetics, RNA Stability, Mitochondrial/metabolism, Exercise/physiology, Drosophila/metabolism, Neoplasm Proteins |
| الوصف: | Decline in mitochondrial function is linked to decreased muscle mass and strength in conditions like sarcopenia and type 2 diabetes. Despite therapeutic opportunities, there is limited and equivocal data regarding molecular cues controlling muscle mitochondrial plasticity. Here we uncovered that the mitochondrial mRNA-stabilizing protein SLIRP, in complex with LRPPRC, is a PGC-1α target that regulates mitochondrial structure, respiration, and mtDNA-encoded-mRNA pools in skeletal muscle. Exercise training effectively counteracts mitochondrial defects caused by genetically-induced LRPPRC/SLIRP loss, despite sustained low mtDNA-encoded-mRNA pools, by increasing mitoribosome translation capacity and mitochondrial quality control. In humans, exercise training robustly increases muscle SLIRP and LRPPRC protein across exercise modalities and sexes, yet less prominently in individuals with type 2 diabetes. SLIRP muscle loss reduces Drosophila lifespan. Our data points to a mechanism of post-transcriptional mitochondrial regulation in muscle via mitochondrial mRNA stabilization, offering insights into how exercise enhances mitoribosome capacity and mitochondrial quality control to alleviate defects. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| DOI: | 10.1038/s41467-024-54183-4 |
| الاتاحة: | https://portal.findresearcher.sdu.dk/da/publications/cd720068-d496-4193-9233-5fcdc9c5e935 https://doi.org/10.1038/s41467-024-54183-4 https://findresearcher.sdu.dk/ws/files/277179845/s41467-024-54183-4.pdf |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.54CCB85D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-024-54183-4 |
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