Phosphorylation of rat brain mitochondrial voltage-dependent anion as a potential tool to control leakage of cytochrome c.
Apoptosis is a controlled form of cell death that participates in development, elimination of damaged cells and maintenance of cell homeostasis. Also, it plays a role in neurodegenerative disorders like Alzheimer's disease. Recently, mitochondria have emerged as being pivotal in controlling apoptosis. They house a number of apoptogenic molecules, such as cytochrome c, which are released into the cytoplasm at the onset of apoptosis. When rat brain mitochondrial voltage-dependent anion channel (VDAC), an outer mitochondrial membrane protein, interacts with Bcl-2 family proteins Bax and tBid, its pore size increases, leading to the release of cytochrome c and other apoptogenic molecules into the cytosol and causing cell death. Regulation of this tBid- and Bax-induced increase in pore size of VDAC is a significant step to control cell death induced by cytochrome c. In this work, we have shown, through bilayer electrophysiological experiments, that the increase in VDAC conductance as a result of its interaction with Bax and tBid is reduced because of the action of cyclic AMP-dependent protein kinase A (PKA) in the presence of ATP. This indicates that the increase in the pore size of VDAC after its interaction with Bax and tBid is controlled via phosphorylation of this channel by PKA. This, we believe, could be a mechanism of controlling cytochrome c-mediated cell death in living cells.
Banerjee
Jyotirmoy
J
Department of Biophysics, University of Delhi South Campus, New Delhi, India.
Ghosh
Subhendu
S
D000818:Animals; D051023:BH3 Interacting Domain Death Agonist Protein / Q000502:physiology; D001921:Brain / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics; D051336:Mitochondrial Membranes / Q000201:enzymology / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D013997:Time Factors; D050994:Voltage-Dependent Anion Channels / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000502:physiology
D051023:BH3 Interacting Domain Death Agonist Protein; D008051:Lipid Bilayers; D050994:Voltage-Dependent Anion Channels; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D017868:Cyclic AMP-Dependent Protein Kinases