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Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors.

Authors
Kagan-VE; Tyurin-VA; Jiang-J; Tyurina-YY; Ritov-VB; Amoscato-AA; Osipov-AN; Belikova-NA; Kapralov-AA; Kini-V; Vlasova-II; Zhao-Q; Zou-M; Di-P; Svistunenko-DA; Kurnikov-IV; Borisenko-GG
Source
Nat Chem Biol 2005 Sep; 1(4):223-232
NIOSHTIC No.
20029429
Abstract
Programmed death (apoptosis) is turned on in damaged or unwanted cells to secure their clean and safe self-elimination. The initial apoptotic events are coordinated in mitochondria, whereby several proapoptotic factors, including cytochrome c, are released into the cytosol to trigger caspase cascades. The release mechanisms include interactions of B-cell/lymphoma 2 family proteins with a mitochondria-specific phospholipid, cardiolipin, to cause permeabilization of the outer mitochondrial membrane. Using oxidative lipidomics, we showed that cardiolipin is the only phospholipid in mitochondria that undergoes early oxidation during apoptosis. The oxidation is catalyzed by a cardiolipin-specific peroxidase activity of cardiolipin-bound cytochrome c. In a previously undescribed step in apoptosis, we showed that oxidized cardiolipin is required for the release of proapoptotic factors. These results provide insight into the role of reactive oxygen species in triggering the cell-death pathway and describe an early role for cytochrome c before caspase activation.
Keywords
Cell-damage; Oxidation; Metabolism; Peptides; Proteins; Laboratory-animals; Animals; Animal-studies
Publication Date
20050901
Document Type
Journal Article
Email Address
vkagan@eoh.pitt.edu
Funding Type
Grant
Fiscal Year
2005
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-008282
Issue of Publication
4
ISSN
1552-4450
Source Name
Nature Chemical Biology
State
PA
Performing Organization
University of Pittsburgh at Pittsburgh
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