Cytochrome C Acts as a Cardiolipin Oxygenase Required for Release of Proapoptotic Factors

Details

• Personal Author:
  Amoscato AA ; Belikova NA ; Borisenko GG ; Di P ; Jiang J ; Kagan VE ; Kapralov AA ; Kini V ; Kurnikov IV ; Osipov AN ; Ritov VB ; Svistunenko DA ; Tyurin VA ; Tyurina YY ; Vlasova II ; Zhao Q ; Zou M
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Animals Energy Metabolism Laboratories Occupational Health Safety
• Keywords:
  Animal-studies Cell-damage Laboratory-animals Metabolism Oxidation Peptides Proteins
• ISSN:
  1552-4450
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  223-232
• Volume:
  1
• Issue:
  4
• NIOSHTIC Number:
  nn:20029429
• Citation:
  Nat Chem Biol 2005 Sep; 1(4):223-232
• Email:
  vkagan@eoh.pitt.edu
• Federal Fiscal Year:
  2005
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Nature Chemical Biology
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6ed49110d7c85b08bd849d73752f33e1729ff8363a7a28e12715abb9e92d192861a72a21b2308fb781d8d55407e5723f8f058d3931c251e67faacdd2e309f65a
• Download URL:
  https://stacks.cdc.gov/view/cdc/190411/cdc_190411_DS1.pdf
• File Type:
  [PDF - 507.88 KB ]