Calcium induced release of mitochondrial cytochrome c by different mechanisms selective for brain versus liver.
Increased mitochondrial Ca2+ accumulation is a trigger for the release of cytochrome c from the mitochondrial intermembrane space into the cytosol where it can activate caspases and lead to apoptosis. This study tested the hypothesis that Ca2+-induced release of cytochrome c in vitro can occur by membrane permeability transition (MPT)-dependent and independent mechanisms, depending on the tissue from which mitochondria are isolated. Mitochondria were isolated from rat liver and brain and suspended at 37 degrees C in a K+-based medium containing oxidizable substrates, ATP, and Mg2+. Measurements of changes in mitochondrial volume (via light scattering and electron microscopy), membrane potential and the medium free [Ca2+] indicated that the addition of 0.3 - 3.2 micromol Ca2+ mg-1 protein induced the MPT in liver but not brain mitochondria. Under these conditions, a Ca2+ dose-dependent release of cytochrome c was observed with both types of mitochondria; however, the MPT inhibitor cyclosporin A was only capable of inhibiting this release from liver mitochondria. Therefore, the MPT is responsible for cytochrome c release from liver mitochondria, whereas an MPT-independent mechanism is responsible for release from brain mitochondria.
Andreyev
A
A
Department of Anesthesiology, University of Maryland, Baltimore School of Medicine, Baltimore, Maryland, 21201, USA.
Fiskum
G
G
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D003574:Cytochrome c Group / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism / Q000502:physiology; D008297:Male; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology; D008930:Mitochondria, Liver / Q000378:metabolism* / Q000502:physiology; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley
D003574:Cytochrome c Group; D002118:Calcium