Death-associated protein kinase as a sensor of mitochondrial membrane potential: role of lysosome in mitochondrial toxin-induced cell death. J Biol Chem 2005 Oct 14;280(41):34644-53
Date
08/09/2005Pubmed ID
16085644DOI
10.1074/jbc.M506466200Scopus ID
2-s2.0-27144458235 (requires institutional sign-in at Scopus site) 36 CitationsAbstract
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.
Author List
Shang T, Joseph J, Hillard CJ, Kalyanaraman BAuthors
Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of WisconsinBalaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
1-Methyl-4-phenylpyridiniumAconitate Hydratase
Antimycin A
Antioxidants
Apoptosis Regulatory Proteins
Calcium-Calmodulin-Dependent Protein Kinases
Cell Death
Cell Line, Tumor
Death-Associated Protein Kinases
Electron Transport
Humans
Lysosomes
Membrane Potentials
Microscopy, Electron
Mitochondrial Membranes
Models, Biological
Phosphatidylinositol 3-Kinases
Phosphorylation
Rotenone
Subcellular Fractions
Tetrazolium Salts
Thiazoles
Time Factors
Toxins, Biological
