Retraction Note to: Exercise-induced mitochondrial p53 repairs mtDNA mutations in mutator mice
| Autor: | Sandeep Raha, Bart P. Hettinga, Tomas A. Prolla, Adam P. W. Johnston, Yevgenya Kratysberg, Imtiaz A. Samjoo, Adeel Safdar, James M. Flynn, Ayesha Saleem, Glenn C. Rowe, Mark A. Tarnopolsky, Yu Kitaoka, Konstantin Khrapko, Daniel I. Ogborn, Zoltan Arany, Michael De Lisio, Jonathan P. Little, Gianni Parise, Mahmood Akhtar |
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| Rok vydání: | 2021 |
| Předmět: |
Genetically modified mouse
Mitochondrial DNA Time Factors lcsh:Diseases of the musculoskeletal system DNA Repair Genotype Apoptosis DNA-Directed DNA Polymerase Mitochondrion Biology Transfection medicine.disease_cause DNA Mitochondrial Genome Mitochondria Heart Life Expectancy Endurance training medicine Animals Orthopedics and Sports Medicine Muscle Skeletal Molecular Biology Cells Cultured Mice Knockout Genetics Mutation Organelle Biogenesis Myocardium Telomere Homeostasis Cell Biology Telomere medicine.disease Myocardial Contraction Mice Mutant Strains DNA Polymerase gamma Mitochondria Muscle Mice Inbred C57BL Oxidative Stress Protein Transport Retraction Note Phenotype Mitochondrial biogenesis Sarcopenia Tumor Suppressor Protein p53 lcsh:RC925-935 Muscle Contraction |
| Zdroj: | Skeletal Muscle, Vol 11, Iss 1, Pp 1-1 (2021) Skeletal Muscle |
| ISSN: | 2044-5040 |
| DOI: | 10.1186/s13395-021-00264-7 |
| Popis: | Human genetic disorders and transgenic mouse models have shown that mitochondrial DNA (mtDNA) mutations and telomere dysfunction instigate the aging process. Epidemiologically, exercise is associated with greater life expectancy and reduced risk of chronic diseases. While the beneficial effects of exercise are well established, the molecular mechanisms instigating these observations remain unclear. Endurance exercise reduces mtDNA mutation burden, alleviates multisystem pathology, and increases lifespan of the mutator mice, with proofreading deficient mitochondrial polymerase gamma (POLG1). We report evidence for a POLG1-independent mtDNA repair pathway mediated by exercise, a surprising notion as POLG1 is canonically considered to be the sole mtDNA repair enzyme. Here, we show that the tumor suppressor protein p53 translocates to mitochondria and facilitates mtDNA mutation repair and mitochondrial biogenesis in response to endurance exercise. Indeed, in mutator mice with muscle-specific deletion of p53, exercise failed to prevent mtDNA mutations, induce mitochondrial biogenesis, preserve mitochondrial morphology, reverse sarcopenia, or mitigate premature mortality. Our data establish a new role for p53 in exercise-mediated maintenance of the mtDNA genome and present mitochondrially targeted p53 as a novel therapeutic modality for diseases of mitochondrial etiology. |
| Databáze: | OpenAIRE |
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