Title

Nitrosylation of cytochrome c during apoptosis

UMMS Affiliation

Department of Medicine

Date

3-21-2003

Document Type

Article

Subjects

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

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

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

10.1074/jbc.M212459200

Related Resources

Link to Article in PubMed

Journal Title

The Journal of biological chemistry

PubMed ID

12646553