The release of cytochrome c from mitochondria during apoptosis of NGF-deprived sympathetic neurons is a reversible event

During apoptosis induced by various stimuli, cytochrome c is released from mitochondria into the cytosol where it participates in caspase activation. This process has been proposed to be an irreversible consequence of mitocho ndrial permeability transition pore opening, which leads to mitochondrial s welling and rupture of the outer mitochondrial membrane. Here we present da ta demonstrating that NGF-deprived sympathetic neurons protected from apopt osis by caspase inhibitors possess mitochondria which, though depleted of c ytochrome c and reduced in size, remained structurally intact as viewed by electron microscopy. After reexposure of neurons to NGF mitochondria recove red their normal size and their cytochrome c content, by a process requirin g de novo protein synthesis. Altogether, these data suggest that depletion of cytochrome c from mitochondria is a controlled process compatible with f unction recovery. The ability of sympathetic neurons to recover fully from trophic factor deprivation provided irreversible caspase inhibitors have be en present during the insult period, has therapeutical implications for a n umber of acute neuropathologies.