title: Phosphorylation of voltage-dependent anion channel by c-Jun N-terminal Kinase-3 leads to closure of the channel.
abstract: Stress activated c-Jun N-terminal Kinase-3 (JNK3) has been reported to act on mitochondrion to promote neuronal cell death. Phosphorylation of mitochondrial Voltage-Dependent Anion Channel (VDAC) plays an important role in mitochondria-mediated cell death. Keeping these in view phosphorylation of rat brain VDAC by JNK3 has been studied in vitro. Pro Q Diamond phospho-protein staining experiment demonstrates VDAC is phosphorylated by JNK3. Bilayer electrophysiological experiments show that single-channel conductance of VDAC phosphorylated by JNK3 is significantly lower than that of the native VDAC at a membrane potential. The opening probability of VDAC undergoes massive reduction due to phosphorylation by JNK3. These indicate closure of VDAC due to phosphorylation by JNK3. Treatment of phosphorylated VDAC with alkaline phosphatase reversed the VDAC functional activity as shown by single-channel current and opening probability. The physiological consequence of closure of VDAC as a result of phosphorylation has been attributed to JNK3 dependent mitochondria-mediated apoptosis.
authors.affiliation: Department of Biophysics, University of Delhi South Campus, New Delhi, India.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Department of Biophysics, University of Delhi South Campus, New Delhi, India. Electronic address: profsubhendu@gmail.com.
authors.forename: Subhendu
authors.initials: S
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D055724:Electrophysiological Phenomena; D008051:Lipid Bilayers / Q000378:metabolism; D048057:Mitogen-Activated Protein Kinase 10 / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism*
chemical_list: D008051:Lipid Bilayers; D050994:Voltage-Dependent Anion Channels; D048057:Mitogen-Activated Protein Kinase 10
keywords: Bilayer electrophysiology; JNK3; Mitochondria-mediated apoptosis; Phosphorylation; VDAC