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

AUTOR(ES)

Smaili, S.S., Hsu, Y.-T., Carvalho, A.C.P., Rosenstock, T.R., Sharpe, J.C., Youle, R.J.

FONTE

Brazilian Journal of Medical and Biological Research

DATA DE PUBLICAÇÃO

2003-02

RESUMO

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.

Documentos Relacionados

• Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals
• p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD
• Gene therapy for carcinoma of the breast: Pro-apoptotic gene therapy
• Targeting of the pro-apoptotic VDAC-like porin (PorB) of Neisseria gonorrhoeae to mitochondria of infected cells
• Pro-apoptotic function of HBV X protein is mediated by interaction with c-FLIP and enhancement of death-inducing signal