Nitrosylation of cytochrome c during apoptosis
Schonhoff, Christopher M. ; Gaston, Benjamin M. ; Mannick, Joan B.
Citations
Student Authors
Faculty Advisor
Academic Program
UMass Chan Affiliations
Document Type
Publication Date
Keywords
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
Subject Area
Embargo Expiration Date
Link to Full Text
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.
Source
J Biol Chem. 2003 May 16;278(20):18265-70. Epub 2003 Mar 19. Link to article on publisher's site