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Cytochrome c/cardiolipin relations in mitochondria: a kiss of death

Kagan, VE and Bayir, HA and Belikova, NA and Kapralov, O and Tyurina, YY and Tyurin, VA and Jiang, J and Stoyanovsky, DA and Wipf, P and Kochanek, PM and Greenberger, JS and Pitt, B and Shvedova, AA and Borisenko, G (2009) Cytochrome c/cardiolipin relations in mitochondria: a kiss of death. Free Radical Biology and Medicine, 46 (11). 1439 - 1453. ISSN 0891-5849

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Recently, phospholipid peroxidation products gained a reputation as key regulatory molecules and participants in oxidative signaling pathways. During apoptosis, a mitochondria-specific phospholipid, cardiolipin (CL), interacts with cytochrome c (cyt c) to form a peroxidase complex that catalyzes CL oxidation; this process plays a pivotal role in the mitochondrial stage of the execution of the cell death program. This review is focused on redox mechanisms and essential structural features of cyt c's conversion into a CL-specific peroxidase that represent an interesting and maybe still unique example of a functionally significant ligand change in hemoproteins. Furthermore, specific characteristics of CL in mitochondria-its asymmetric transmembrane distribution and mechanisms of collapse, the regulation of its synthesis, remodeling, and fatty acid composition-are given significant consideration. Finally, new concepts in drug discovery based on the design of mitochondria-targeted inhibitors of cyt c/CL peroxidase and CL peroxidation with antiapoptotic effects are presented.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Kagan, VEkagan@pitt.eduKAGAN
Bayir, HAhub22@pitt.eduHUB220000-0003-2361-4120
Belikova, NA
Kapralov, O
Tyurina, YY
Tyurin, VA
Jiang, Jjjf73@pitt.eduJJF73
Stoyanovsky, DAdas11@pitt.eduDAS110000-0001-5591-4780
Wipf, Ppwipf@pitt.eduPWIPF
Kochanek, PMkochanekpm@pitt.eduPAK60000-0002-2627-913X
Greenberger, JSjoelg@pitt.eduJOELG
Pitt, Bbrucep@pitt.eduBRUCEP
Shvedova, AA
Borisenko, G
Date: 1 June 2009
Date Type: Publication
Journal or Publication Title: Free Radical Biology and Medicine
Volume: 46
Number: 11
Page Range: 1439 - 1453
DOI or Unique Handle: 10.1016/j.freeradbiomed.2009.03.004
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Refereed: Yes
ISSN: 0891-5849
Article Type: Review
MeSH Headings: Animals; Apoptosis; Cardiolipins--physiology; Cytochromes c--physiology; Humans; Lipid Peroxidation--physiology; Mitochondria--physiology; Oxidative Stress; Protein Binding; Signal Transduction
Other ID: NLM NIHMS102249, NLM PMC2732771
PubMed Central ID: PMC2732771
PubMed ID: 19285551
Date Deposited: 12 Jun 2013 20:31
Last Modified: 16 Sep 2020 13:55


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