Premium
Caspase‐dependent alteration of the ADP/ATP translocator triggers the mitochondrial permeability transition which is not required for the low‐potassium‐dependent apoptosis of cerebellar granule cells
Author(s) -
Atlante Anna,
Bobba Antonella,
De Bari Lidia,
Fontana Fabrizio,
Calissano Pietro,
Marra Ersilia,
Passarella Salvatore
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03820.x
Subject(s) - mitochondrial permeability transition pore , adenine nucleotide translocator , cytochrome c , apoptosis , translocator protein , microbiology and biotechnology , atp–adp translocase , mitochondrion , biochemistry , biophysics , biology , programmed cell death , chemistry , inner mitochondrial membrane , immunology , neuroinflammation , inflammation
We investigated ADP/ATP exchange mediated by the adenine nucleotide translocator and opening of the mitochondrial permeability transition pore in homogenates from cerebellar granule cells en route to apoptosis induced by low potassium. We showed that, in the first 3 h of apoptosis, when maximum cytochrome c release had already occurred, adenine nucleotide translocator function was impaired owing to the action of reactive oxygen species, but no permeability transition pore opening occurred. Over 3–8 h of apoptosis, the permeability transition pore progressively opened, owing to caspase action, and further ADP/ATP translocator impairment occurred. The kinetics of transport and permeability transition pore opening were inversely correlated, both in the absence and presence of inhibitors of antioxidant and proteolytic systems. We conclude that, en route to apoptosis, alteration of the adenine nucleotide translocator occurs, resulting in permeability transition pore opening. This process depends on the action of caspase on pore component(s) other than the ADP/ATP translocator, because no change in either amount or molecular weight of the latter protein was noted during apoptosis, as measured by western blotting. Cell death occurs via apoptosis in the presence of cyclosporin A, the permeability transition pore inhibitor, thus showing that permeability transition pore opening, not needed for cytochrome c release, is also unnecessary for apoptosis to occur.