Nitrosylation of cytochrome c during apoptosis
Department of Medicine
Acridine Orange; Animals; Antigens, CD95; *Apoptosis; Caspase 3; Caspases; Cell Line; Cytochrome c Group; Fluorescent Dyes; Heme; Horses; Humans; Iron; Nitrogen; Precipitin Tests; Proto-Oncogene Proteins c-bcl-2; Signal Transduction; Spectrophotometry; Time Factors; Ultraviolet Rays; bcl-X Protein
Life Sciences | Medicine and Health Sciences
Cytochrome c released from mitochondria into the cytoplasm plays a critical role in many forms of apoptosis by stimulating apoptosome formation and subsequent caspase activation. However, the mechanisms regulating cytochrome c apoptotic activity are not understood. Here we demonstrate that cytochrome c is nitrosylated on its heme iron during apoptosis. Nitrosylated cytochrome c is found predominantly in the cytoplasm in control cells. In contrast, when cytochrome c release from mitochondria is inhibited by overexpression of the anti-apoptotic proteins B cell lymphoma/leukemia (Bcl)-2 or Bcl-X(L), nitrosylated cytochrome c is found in the mitochondria. These data suggest that during apoptosis, cytochrome c is nitrosylated in mitochondria and then rapidly released into the cytoplasm in the absence of Bcl-2 or Bcl-X(L) overexpression. In vitro nitrosylation of cytochrome c increases caspase-3 activation in cell lysates. Moreover, the inhibition of intracellular cytochrome c nitrosylation is associated with a decrease in apoptosis, suggesting that cytochrome c nitrosylation is a proapoptotic modification. We conclude that nitrosylation of the heme iron of cytochrome c may be a novel mechanism of apoptosis regulation.
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Citation: J Biol Chem. 2003 May 16;278(20):18265-70. Epub 2003 Mar 19. Link to article on publisher's site
DOI of Published Version
The Journal of biological chemistry
Schonhoff, Christopher M.; Gaston, Benjamin M.; and Mannick, Joan B., "Nitrosylation of cytochrome c during apoptosis" (2003). Open Access Articles. 720.