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DNA Polymerase Gamma Acetylation Governs Mitochondrial Homeostasis and Vascular Cell Senescence - PubMed

2 days ago
  • #mitochondrial homeostasis
  • #DNA polymerase gamma
  • #vascular aging
  • DNA polymerase gamma (Polγ) is crucial for mitochondrial DNA (mtDNA) replication and metabolism-associated senescence.
  • Lysine acetylation at K1039 on Polγ is dynamically regulated during aging and affects mitochondrial function.
  • Hyper-acetylation of Polγ K1039 reduces human aortic smooth muscle cell (HASMC) contractility and leads to hyperproliferation and mitochondrial dysfunction.
  • D257A mutation in Polγ disrupts Sirt3-Polγ complex formation, leading to aberrant acetylation homeostasis and cellular senescence.
  • Polγ acetylation at K1039 acts as a molecular switch for mtDNA homeostasis, HASMC functionality, and senescence progression.
  • The findings provide insights into epigenetic-metabolic crosstalk in vascular aging and age-related pathologies.