title: Mitochondria, calcium and pro-apoptotic proteins as mediators in cell death signaling.
abstract: Cellular Ca2+ signals are crucial in the control of most physiological processes, cell injury and programmed cell death through the regulation of a number of Ca2+-dependent enzymes such as phospholipases, proteases, and nucleases. Mitochondria along with the endoplasmic reticulum play pivotal roles in regulating intracellular Ca2+ content. Mitochondria are endowed with multiple Ca2+ transport mechanisms by which they take up and release Ca2+ across their inner membrane. During cellular Ca2+ overload, mitochondria take up cytosolic Ca2+, which in turn induces opening of permeability transition pores and disrupts the mitochondrial membrane potential (deltapsim). The collapse of deltapsim along with the release of cytochrome c from mitochondria is followed by the activation of caspases, nuclear fragmentation and cell death. Members of the Bcl-2 family are a group of proteins that play important roles in apoptosis regulation. Members of this family appear to differentially regulate intracellular Ca2+ level. Translocation of Bax, an apoptotic signaling protein, from the cytosol to the mitochondrial membrane is another step in this apoptosis signaling pathway.
authors.affiliation: Departamento de Farmacologia, Instituto de Farmacologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
authors.forename: S S
authors.initials: SS
authors.lastname: Smaili
authors.forename: Y-T
authors.initials: YT
authors.lastname: Hsu
authors.forename: A C P
authors.initials: AC
authors.lastname: Carvalho
authors.forename: T R
authors.initials: TR
authors.lastname: Rosenstock
authors.forename: J C
authors.initials: JC
authors.lastname: Sharpe
authors.forename: R J
authors.initials: RJ
authors.lastname: Youle
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D008222:Lymphokines / Q000502:physiology*; D008928:Mitochondria / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D051028:bcl-2-Associated X Protein
chemical_list: D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein