title: The multiple functions of cytochrome c and their regulation in life and death decisions of the mammalian cell: From respiration to apoptosis.
abstract: 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.
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA. mhuttema@med.wayne.edu
authors.forename: Maik
authors.initials: M
authors.lastname: Hüttemann
authors.forename: Petr
authors.initials: P
authors.lastname: Pecina
authors.forename: Matthew
authors.initials: M
authors.lastname: Rainbolt
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Sanderson
authors.forename: Valerian E
authors.initials: VE
authors.lastname: Kagan
authors.forename: Lobelia
authors.initials: L
authors.lastname: Samavati
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Doan
authors.forename: Icksoo
authors.initials: I
authors.lastname: Lee
mesh_terms: D017209:Apoptosis; D019069:Cell Respiration; D045304:Cytochromes c / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000201:enzymology* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D028361:Mitochondrial Diseases
chemical_list: D045304:Cytochromes c