The “Pro-Apoptotic Genies” Get Out of Mitochondria: Oxidative Lipidomics and Redox Activity of Cytochrome C/Cardiolipin Complexes

Details

• Personal Author:
  Amoscato A ; Bayir H ; Belikova NA ; Chu CT ; Dekosky S ; Epperly M ; Greenberger J ; Jiang J ; Kagan VE ; Kapralov AA ; Shvedova AA ; Tyurin VA ; Tyurina YY ; Vlasova II
• Description:
  One of the prominent consequences of the symbiogenic origin of eukaryotic cells is the unique presence of one particular class of phospholipids, cardiolipin (CL), in mitochondria. As the product originated from the evolution of symbiotic bacteria, CL is predominantly confined to the inner mitochondrial membrane in normally functioning cells. Recent findings identified CL and its oxidation products as important participants and signaling molecules in the apoptotic cell death program. Early in apoptosis, massive membrane translocations of CL take place resulting in its appearance in the outer mitochondrial membrane. Consequently, significant amounts of CL become available for the interactions with cyt c, one of the major proteins of the intermembrane space. Binding of CL with cytochrome c (cyt c) yields the cyt c/CL complex that acts as a potent CL-specific peroxidase and generates CL hydroperoxides. In this review, we discuss the catalytic mechanisms of CL oxidation by the peroxidase activity of cyt c as well as the role of oxidized CL (CLox) in the release of pro-apoptotic factors from mitochondria into the cytosol. Potential implications of cyt c/CL peroxidase intracellular complexes in disease conditions (cancer, neurodegeneration) are also considered. The discovery of the new role of cyt c/CL complexes in early mitochondrial apoptosis offers interesting opportunities for new targets in drug discovery programs. Finally, exit of cyt c from damaged and/or dying (apoptotic) cells into extracellular compartments and its accumulation in biofluids is discussed in lieu of the formation of its peroxidase complexes with negatively charged lipids and their significance in the development of systemic oxidative stress in circulation. [Description provided by NIOSH]
• Subjects:
  Lipids Occupational Health Safety
• Keywords:
  Bacteria Cell-function Diseases Hydroperoxides Oxidation Oxidation-reduction-reactions Peroxidases Phospholipids Proteins
• ISSN:
  0009-2797
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  15-28
• Volume:
  163
• Issue:
  1
• NIOSHTIC Number:
  nn:20031141
• Citation:
  Chem-Biol Interact 2006 Oct; 163(1-2):15-28
• Contact Point Address:
  Center for Free Radical & Antioxidant Health, Department of EOH, University of Pittsburgh, Bridgeside Point, 100 Technology Drive, Suite 350, Pittsburgh, PA 15219, USA
• Email:
  vkagan@eoh.pitt.edu
• Federal Fiscal Year:
  2007
• NORA Priority Area:
  Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Chemico-Biological Interactions
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:871f31d9cb3c6a8677f0ad4be884c31bbaa6e6089ab0ea4e3d2383756a80aa3a64e7300a69915b2ba1fba4bc1ce8b8ad4f532dbee71178b611468604b79be215
• Download URL:
  https://stacks.cdc.gov/view/cdc/191483/cdc_191483_DS1.pdf
• File Type:
  [PDF - 667.71 KB ]