Mitochondrial phosphatase PGAM5 modulates cellular senescence by regulating mitochondrial dynamics

Bo Yu, Jing Ma, Jing Li, Dazhi Wang, Zhigao Wang, Shusheng Wang

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


Mitochondria undergo dynamic fusion/fission, biogenesis and mitophagy in response to stimuli or stresses. Disruption of mitochondrial homeostasis could lead to cell senescence, although the underlying mechanism remains unclear. We show that deletion of mitochondrial phosphatase PGAM5 leads to accelerated retinal pigment epithelial (RPE) senescence in vitro and in vivo. Mechanistically, PGAM5 is required for mitochondrial fission through dephosphorylating DRP1. PGAM5 deletion leads to increased mitochondrial fusion and decreased mitochondrial turnover. As results, cellular ATP and reactive oxygen species (ROS) levels are elevated, mTOR and IRF/IFN-β signaling pathways are enhanced, leading to cellular senescence. Overexpression of Drp1 K38A or S637A mutant phenocopies or rescues mTOR activation and senescence in PGAM5−/− cells, respectively. Young but not aging Pgam5−/− mice are resistant to sodium iodate-induced RPE cell death. Our studies establish a link between defective mitochondrial fission, cellular senescence and age-dependent oxidative stress response, which have implications in age-related diseases.

Original languageEnglish (US)
Article number2549
JournalNature communications
Issue number1
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


Dive into the research topics of 'Mitochondrial phosphatase PGAM5 modulates cellular senescence by regulating mitochondrial dynamics'. Together they form a unique fingerprint.

Cite this