Mitochondria, calcium and pro-apoptotic proteins as mediators in cell death signaling

• Published in: Brazilian journal of medical and biological research Vol. 36; no. 2; pp. 183 - 190
• Main Authors: Smaili, S S, Hsu, Y-T, Carvalho, A C P, Rosenstock, T R, Sharpe, J C, Youle, R J
• Format: Journal Article
• Language: English
• Published: Brazil Associação Brasileira de Divulgação Científica 01.02.2003
• Subjects: Animals; Apoptosis; Apoptosis - physiology; Bax and apoptosis; Bcl-2 family; bcl-2-Associated X Protein; Ca2; Calcium Signaling - physiology; Lymphokines - physiology; Mitochondria - physiology; Mitochondrial Ca2+ efflux; Mitochondrial Ca2+ uptake; Permeability transition; Proto-Oncogene Proteins - physiology; Proto-Oncogene Proteins c-bcl-2 - physiology
• ISSN: 0100-879X; 0100-879X; 1414-431X
• DOI: 10.1590/S0100-879X2003000200004

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.