Cytochrome c/cardiolipin relations in mitochondria: a kiss of death.
Kagan-VE; Bayir-HA; Belikova-NA; Kapralov-O; Tyurina-YY; Tyurin-VA; Jiang-JF; Stoyanovsky-DA; Wipf-P; Kochanek-PM; Greenberger-JS; Pitt-B; Shvedova-AA; Borisenko-G
Free Radic Biol Med 2009 Jun; 46(11):1439-1453
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.
Cell-biology; Cell-growth; Cell-metabolism; Cell-morphology; Cellular-reactions; Humans; Oxidative-metabolism; Oxidative-processes;
Author Keywords: Cytochrome c; Cardiolipin; Peroxidase; Lipidomics; Oxidative stress; Apoptosis; Autophagy; Mitochondrial targeting; Free radicals
VE Kagan, Ctr Free Rad & Antioxidant Hlth, Pittsburgh, PA 15219
Free Radical Biology and Medicine