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 language | English (US) |
---|---|
Pages (from-to) | 34644-34653 |
Number of pages | 10 |
Journal | Journal of Biological Chemistry |
Volume | 280 |
Issue number | 41 |
DOIs | |
State | Published - Oct 14 2005 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology