RETRACTED ARTICLE:Exercise-induced mitochondrial p53 repairs mtDNA mutations in mutator mice
Authors: Michael De Lisio
James M Flynn
Konstantin Khrapko
Yu Kitaoka
Daniel I Ogborn
Ayesha Saleem
Mahmood Akhtar
Jonathan P Little
Yevgenya Kratysberg
Mark A Tarnopolsky
Glenn C Rowe
Adeel Safdar
Zoltan Arany
Adam P W Johnston
Sandeep Raha
Bart P Hettinga
Tomas A Prolla
Imtiaz A Samjoo
Gianni Parise
Journal: Skeletal Muscle (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Apoptosis; Endurance exercise; Mitochondrial DNA mutations; Mutator mouse; Oxidative stress
Affiliations: Department of Kinesiology, McMaster University, Hamilton, ON L8N 3Z5 Canada ; Department of Pediatrics, McMaster University, Hamilton, ON L8N 3Z5 Canada ; Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5 Canada., Northeastern University, Boston, MA 02115 USA., Buck Institute for Research on Aging, Novato, CA 94945 USA., Department of Pediatrics, McMaster University, Hamilton, ON L8N 3Z5 Canada., Department of Kinesiology, McMaster University, Hamilton, ON L8N 3Z5 Canada., Department of Medical Sciences, McMaster University, Hamilton, ON L8N 3Z5 Canada., School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, BC V1V 1V7 Canada., Department of Kinesiology, McMaster University, Hamilton, ON L8N 3Z5 Canada ; Department of Medical Physics & Applied Radiation Sciences, McMaster University, Hamilton, ON L8N 3Z5 Canada., Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5 Canada., Division of Cardiovascular Disease, University of Alabama, Birmingham, AL 35294 USA., Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA., Departments of Genetics, University of Wisconsin, Madison, WI 53706 USA ; Departments of Medical Genetics, University of Wisconsin, Madison, WI 53706 USA., Department of Pediatrics, McMaster University, Hamilton, ON L8N 3Z5 Canada ; Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5 Canada.

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. 

Retracted: Yes

PubPeer comments:
 2021 retraction. https: skeletalmusclejournal.biomedcentral.com articles 10.1186 s13395-021-00264-7 The Editors-in-Chief have retracted this article. Following concerns raised by the corresponding author, an investigation by McMaster University confirmed concerns with Figs. 3 and 4 of this article, specifically: Figure 3b: the VDAC band appears to be identical with the Actin band of Fig. 3b of the original article Figure 4d overlaps with Fig. 4b of the original article The Editors therefore no longer have confidence in the reliability of the data reported in the article. Adeel Safdar, Konstantin Khrapko, Ayesha Saleem, Michael De Lisio, Adam P. W. Johnston, Imtiaz A. Samjoo, Yu Kitaoka, Daniel I. Ogborn, Jonathan P. Little, Sandeep Raha, Gianni Parise, Mahmood Akhtar, Bart P. Hettinga, Glenn C. Rowe, Zoltan Arany and Mark A. Tarnopolsky agree to this retraction. James M. Flynn, Yevgenya Kratysberg and Tomas A. Prolla have not responded to correspondence about this retraction. , 
 See also https: retractionwatch.com 2021 04 07 researcher-charged-with-abusing-his-wife-has-third-paper-retracted ,