Ascenzi Paolo, Coletta Massimo, Wilson Michael T, Fiorucci Laura, Marino Maria, Polticelli Fabio, Sinibaldi Federica, Santucci Roberto
Interdepartmental Laboratory for Electron Microscopy, Roma Tre University, Roma, Italy.
IUBMB Life. 2015 Feb;67(2):98-109. doi: 10.1002/iub.1350. Epub 2015 Apr 9.
Cytochrome c (cytc) is a small heme-protein located in the space between the inner and the outer membrane of the mitochondrion that transfers electrons from cytc-reductase to cytc-oxidase. The hexa-coordinated heme-Fe atom of cytc displays a very low reactivity toward ligands and does not exhibit significant catalytic properties. However, upon cardiolipin (CL) binding, cytc achieves ligand binding and catalytic properties reminiscent of those of myoglobin and peroxidase. In particular, the peroxidase activity of the cardiolipin-cytochrome c complex (CL-cytc) is critical for the redistribution of CL from the inner to the outer mitochondrial membranes and is essential for the execution and completion of the apoptotic program. On the other hand, the capability of CL-cytc to bind NO and CO and the heme-Fe-based scavenging of reactive nitrogen and oxygen species may affect apoptosis. Here, the ligand binding and catalytic properties of CL-cytc are analyzed in parallel with those of CL-free cytc, myoglobin, and peroxidase to dissect the potential mechanisms of CL in modulating the pro- and anti-apoptotic actions of cytc.
细胞色素c(cytc)是一种小的血红素蛋白,位于线粒体内膜和外膜之间的空间中,它将电子从细胞色素c还原酶传递给细胞色素c氧化酶。细胞色素c的六配位血红素铁原子对配体的反应性非常低,并且不表现出显著的催化特性。然而,在与心磷脂(CL)结合后,细胞色素c获得了类似于肌红蛋白和过氧化物酶的配体结合和催化特性。特别地,心磷脂 - 细胞色素c复合物(CL - cytc)的过氧化物酶活性对于心磷脂从线粒体内膜向外膜的重新分布至关重要,并且对于凋亡程序的执行和完成必不可少。另一方面,CL - cytc结合一氧化氮和一氧化碳的能力以及基于血红素铁的活性氮和氧物种清除可能会影响细胞凋亡。在这里,将CL - cytc的配体结合和催化特性与无CL的细胞色素c、肌红蛋白和过氧化物酶的特性进行平行分析,以剖析CL调节细胞色素c促凋亡和抗凋亡作用的潜在机制。