Death-associated protein kinase as a sensor of mitochondrial membrane potential: Role of lysosome in mitochondrial toxin-induced cell death

Tiesong Shang, Joy Joseph, Cecilia J. Hillard, B. Kalyanaraman

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

We have investigated here the mechanism of dephosphorylation and activation of death-associated protein kinase (DAPK) and the role of lysosome in neuroblastoma cells (SH-SY5Y) treated with mitochondrial toxins, such as MPP+ and rotenone. Mitochondrial respiratory chain inhibitors and uncouplers decreased mitochondrial membrane potential leading to DAPK dephosphorylation and activation. The class III phosphoinositide 3-kinase inhibitors attenuated DAPK dephosphorylation induced by mitochondrial toxins. Complex I inhibition by mitochondrial toxins (e.g. MPP+) resulted in mitochondrial swelling and lysosome reduction. Inhibition of class III phosphoinositide 3-kinase attenuated MPP+-induced lysosome reduction and cell death. The role of DAPK as a sensor of mitochondrial membrane potential in mitochondrial diseases was addressed.

Original languageEnglish (US)
Pages (from-to)34644-34653
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number41
DOIs
StatePublished - Oct 14 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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