The multiple functions of cytochrome c and their regulation in life and death decisions of the mammalian cell: from respiration to apoptosis.
Huttemann-M; Pecina-P; Rainbolt-M; Sanderson-TH; Kagan-VE; Samavati-L; Doan-JW; Lee-I
Mitochondrion 2011 May; 11(3):369-381
Cytochrome c (Cytc) is essential in mitochondrial electron transport and intrinsic type II apoptosis. Mammalian Cytc also scavenges reactive oxygen species (ROS) under healthy conditions, produces ROS with the co-factor p66(Shc), and oxidizes cardiolipin during apoptosis. The recent finding that Cytc is phosphorylated in vivo underpins a model for the pivotal role of Cytc regulation in making life and death decisions. An apoptotic sequence of events is proposed involving changes in Cytc phosphorylation, increased ROS via increased mitochondrial membrane potentials or the p66(Shc) pathway, and oxidation of cardiolipin by Cytc followed by its release from the mitochondria. Cytc regulation in respiration and cell death is discussed in a human disease context including neurodegenerative and cardiovascular diseases, cancer, and sepsis.
Cell-biology; Cell-cultures; Cell-damage; Cell-function; Cancer; Cardiovascular-disease; Cardiovascular-system-disease; Mammalian-cells;
Author Keywords: Aging; Apoptosis; Cardiolipin; Cell signaling; Cytochrome c; Oxidative phosphorylation; Reactive oxygen species
Petr Pecina, Institute of Physiology and Center for Applied Genomics, Academy of Sciences of the Czech Republic, Vídenská 1083, Prague, Czech Republic
University of Pittsburgh at Pittsburgh