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

• Autor(a) principal: Smaili, Soraya Soubhi [UNIFESP]
• Data de Publicação: 2003
• Outros Autores: Hsu, Y.-t., Carvalho, A.c.p. [UNIFESP], Rosenstock, T.r. [UNIFESP], Sharpe, J.c., Youle, R.j.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1590/S0100-879X2003000200004; http://repositorio.unifesp.br/handle/11600/1657
• topic: Ca2+; Mitochondrial Ca2+ uptake; Mitochondrial Ca2+ efflux; Permeability transition; Apoptosis; Bcl-2 family; Bax and apoptosis

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 (Dym). The collapse of Dym 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.