Login / Signup

TRAP1 inhibits MIC60 ubiquitination to mitigate the injury of cardiomyocytes and protect mitochondria in extracellular acidosis.

Lingxiao ZhangNing SuYuanyuan LuoSiyin ChenTongfeng Zhao
Published in: Cell death discovery (2021)
Extracellular acidosis-induced mitochondrial damage of cardiomyocytes leads to cardiac dysfunction, but no detailed mechanism or efficient therapeutic target has been reported. Here we found that the protein levels of MIC60 were decreased in H9C2 cells and heart tissues in extracellular acidosis, which caused mitochondrial damage and cardiac dysfunction. Overexpression of MIC60 maintains H9C2 cells viability, increases ATP production and mitochondrial membrane potential, mitigates the disruptions of mitochondrial structure and cardiac injury. Mechanistically, extracellular acidosis excessively promoted MIC60 ubiquitin-dependent degradation. TRAP1 mitigated acidosis-induced mitochondrial impairments and cardiac injury by directly interacting with MIC60 to decrease its ubiquitin-dependent degradation in extracellular acidosis.
Keyphrases
  • oxidative stress
  • induced apoptosis
  • diabetic rats
  • high glucose
  • left ventricular
  • cell cycle arrest
  • small molecule
  • cell proliferation
  • cell death
  • signaling pathway
  • transcription factor
  • protein kinase