The Release of Cytochrome c from Mitochondria during Apoptosis of NGF-Deprived Sympathetic Neurons Is a Reversible Event

• Published in: The Journal of cell biology Vol. 144; no. 5; pp. 883 - 889
• Main Authors: Martinou, Isabelle, Desagher, Solange, Eskes, Robert, Antonsson, Bruno, André, Elisabeth, Fakan, Stanislav, Martinou, Jean-Claude
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 08.03.1999; The Rockefeller University Press
• Subjects: Amino Acid Chloromethyl Ketones - pharmacology; Animals; Apoptosis; Caspase Inhibitors; Cell death; Cell lines; Cells; Cells, Cultured; Cellular biology; Cysteine Proteinase Inhibitors - pharmacology; Cytochrome c Group - metabolism; Cytochromes; Electron microscopy; Mice; Microscopy, Electron; Mitochondria; Mitochondria, Liver - drug effects; Mitochondria, Liver - enzymology; Mitochondria, Liver - ultrastructure; Nerve Growth Factors - metabolism; Nerve Growth Factors - pharmacology; Neurites; Neurons; Neurons - cytology; Neurons - ultrastructure; Regular; Swelling; Sympathetic Nervous System - cytology
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.144.5.883

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 mitochondrial permeability transition pore opening, which leads to mitochondrial swelling and rupture of the outer mitochondrial membrane. Here we present data demonstrating that NGF-deprived sympathetic neurons protected from apoptosis by caspase inhibitors possess mitochondria which, though depleted of cytochrome c and reduced in size, remained structurally intact as viewed by electron microscopy. After reexposure of neurons to NGF, mitochondria recovered their normal size and their cytochrome c content, by a process requiring de novo protein synthesis. Altogether, these data suggest that depletion of cytochrome c from mitochondria is a controlled process compatible with function recovery. The ability of sympathetic neurons to recover fully from trophic factor deprivation provided irreversible caspase inhibitors have been present during the insult period, has therapeutical implications for a number of acute neuropathologies.