Drp1 dephosphorylation in ATP depletion-induced mitochondrial injury and tubular cell apoptosis

Sung Gyu Cho, Quansheng Du, Shuang Huang, Zheng Dong

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Recent studies revealed a striking morphological change of mitochondria during apoptosis. Mitochondria become fragmented and notably, the fragmentation contributes to mitochondrial outer membrane permeabilization and consequent release of apoptotic factors. In renal tubular cells, mitochondrial fragmentation involves the activation of Drp1, a key mitochondrial fission protein. However, it is unclear how Drp1 is regulated during tubular cell apoptosis. In this study, we examined Drp1 regulation during tubular cell apoptosis following ATP depletion. Rat kidney proximal tubular cells (RPTC) were subjected to azide treatment or severe hypoxia in glucose-free medium to induce ATP depletion. During ATP depletion, Drp1 was shown to be dephosphorylated at serine-637. Drp1 dephosphorylation could be suppressed by cyclosporine A and FK506, two calcineurin inhibitors. Importantly, cyclosporine A and FK506 could also prevent mitochondrial fragmentation, Bax accumulation, cytochrome c release, and apoptosis following ATP depletion in RPTC. The results suggest that calcineurin-mediated serine-637 dephosphorylation is involved in Drp1 activation during ATP depletion in renal tubular cells. Upon activation, Drp1 contributes to mitochondrial fragmentation and outer membrane permeabilization, resulting in the release of apoptogenic factors and apoptosis.

Original languageEnglish (US)
Pages (from-to)F199-F206
JournalAmerican Journal of Physiology - Renal Physiology
Issue number1
StatePublished - Jul 2010


  • Bax
  • Calcineurin
  • Cyclosporine A
  • Cytochrome c
  • FK506
  • Mitochondrial dynamics

ASJC Scopus subject areas

  • Physiology
  • Urology


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