RETRACTED ARTICLE:Exercise-induced mitochondrial p53 repairs mtDNA mutations in mutator mice
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A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Post-publication record
- Nature
- Retraction
- Reason
- Duplication of/in Image;Investigation by Company/Institution;
- Date
- 3/30/2021 0:00
- Flagged by OpenAlex?
- Yes
Source: Retraction Watch, joined by DOI. OpenAlex records retraction as is_retracted, a boolean over a state space with at least four values, so it cannot express an expression of concern, a correction or a reinstatement — it reports them as false, which reads as “fine”.
Abstract
BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.
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The record
- Venue
- Skeletal Muscle
- Topic
- Mitochondrial Function and Pathology
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- Okanagan University CollegeUniversity of British Columbia, Okanagan CampusUniversity of British ColumbiaMcMaster University Medical CentreMcMaster University
- Funders
- National Institute on AgingUnited Mitochondrial Disease FoundationCanadian Institutes of Health ResearchInstitute of Musculoskeletal Health and ArthritisNatural Sciences and Engineering Research Council of CanadaMcMaster UniversityNational Institutes of HealthEllison Medical Foundation
- Keywords
- Mitochondrial DNAGeneticsBiologyComputational biologyBioinformaticsGene
- Has abstract in OpenAlex
- yes