Details

Autor(en) / Beteiligte

• Kagan, Valerian E.
• Bayır, Hülya A.
• Belikova, Natalia A.
• Kapralov, Olexandr
• Tyurina, Yulia Y.
• Tyurin, Vladimir A.
• Jiang, Jianfei
• Stoyanovsky, Detcho A.
• Wipf, Peter
• Kochanek, Patrick M.
• Greenberger, Joel S.
• Pitt, Bruce
• Shvedova, Anna A.
• Borisenko, Grigory

Titel

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

Ist Teil von

• Free radical biology & medicine, 2009-06, Vol.46 (11), p.1439-1453

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2009

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• 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.