Cardiolipin Switch in Mitochondria: Shutting Off the Reduction of Cytochrome C and Turning On the Peroxidase Activity

Details

• Personal Author:
  Basova LV ; Bayir H ; Belikova NA ; Kagan VE ; Kurnikov IV ; Pacheco AA ; Peterson J ; Ritov VB ; Vlasova II ; Waldeck DH ; Wang L ; Winnica DE
• Description:
  Upon interaction with anionic phospholipids, particularly mitochondria-specific cardiolipin (CL), cytochrome c (cyt c) loses its tertiary structure and its peroxidase activity dramatically increases. CL-induced peroxidase activity of cyt c has been found to be important for selective CL oxidation in cells undergoing programmed death. During apoptosis, the peroxidase activity and the fraction of CL-bound cyt c markedly increase, suggesting that CL may act as a switch to regulate cyt c's mitochondrial functions. Using cyclic voltammetry and equilibrium redox titrations, we show that the redox potential of cyt c shifts negatively by 350-400 mV upon binding to CL-containing membranes. Consequently, functions of cyt c as an electron transporter and cyt c reduction by Complex III are strongly inhibited. Further, CL/cyt c complexes are not effective in scavenging superoxide anions and are not effectively reduced by ascorbate. Thus, both redox properties and functions of cyt c change upon interaction with CL in the mitochondrial membrane, diminishing cyt c's electron donor/acceptor role and stimulating its peroxidase activity. [Description provided by NIOSH]
• Subjects:
  Electrophysiology Energy Metabolism Enzymes Lipids Occupational Health Safety
• Keywords:
  Cell-metabolism Cellular-structures Cellular-transport-mechanism Enzyme-activity Lipid-peroxidation Metabolism Oxidation Oxidation-reduction-reactions Pharmacology
• ISSN:
  0006-2960
• 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
• Volume:
  46
• Issue:
  11
• NIOSHTIC Number:
  nn:20032008
• Citation:
  Biochemistry 2007 Mar; 46(11):3423-3434
• Contact Point Address:
  Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260
• CAS Registry Number:
  2,7-Dichlorodihydrofluorescein (CAS RN 106070-31-9) ; Acridine Orange (CAS RN 65-61-2) ; Cytochrome c (CAS RN 9007-43-6) ; DOPC (CAS RN 10015-85-7) ; Etoposide (CAS RN 33419-42-0) ; L-Tryptophan (CAS RN 73-22-3)
• Federal Fiscal Year:
  2007
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Biochemistry
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:360aa0a35e9b5c0e2edbaef5f6e987057b991d81b0cd68f5c8c22cb32c97ec1a9e9be85fd70609cd6b294c30bdc1bcaad3717c2fb137b98dc9919896729e2328
• Download URL:
  https://stacks.cdc.gov/view/cdc/186102/cdc_186102_DS1.pdf
• File Type:
  [PDF - 225.27 KB ]