Data/hora: 06/06/2024 00:21:51

Provedor de dados: | 56
País: | Brazil
Título: | A mechanistic view of mitochondrial death decision pores
Autores: | Belizário,J.E.; Alves,J.; Occhiucci,J.M.; Garay-Malpartida,M.; Sesso,A.
Data: | 2007-08-01
Ano: | 2007
Palavras-chave: | Mitochondrial outer membrane permeabilization; Permeability transition pore; Cytochrome c; Reactive oxygen species; Caspases; BCL-2.
Resumo: | Mitochondria increase their outer and inner membrane permeability to solutes, protons and metabolites in response to a variety of extrinsic and intrinsic signaling events. The maintenance of cellular and intraorganelle ionic homeostasis, particularly for Ca2+, can determine cell survival or death. Mitochondrial death decision is centered on two processes: inner membrane permeabilization, such as that promoted by the mitochondrial permeability transition pore, formed across inner membranes when Ca2+ reaches a critical threshold, and mitochondrial outer membrane permeabilization, in which the pro-apoptotic proteins BID, BAX, and BAK play active roles. Membrane permeabilization leads to the release of apoptogenic proteins: cytochrome c, apoptosis-inducing factor, Smac/Diablo, HtrA2/Omi, and endonuclease G. Cytochrome c initiates the proteolytic activation of caspases, which in turn cleave hundreds of proteins to produce the morphological and biochemical changes of apoptosis. Voltage-dependent anion channel, cyclophilin D, adenine nucleotide translocase, and the pro-apoptotic proteins BID, BAX, and BAK may be part of the molecular composition of membrane pores leading to mitochondrial permeabilization, but this remains a central question to be resolved. Other transporting pores and channels, including the ceramide channel, the mitochondrial apoptosis-induced channel, as well as a non-specific outer membrane rupture may also be potential release pathways for these apoptogenic factors. In this review, we discuss the mechanistic models by which reactive oxygen species and caspases, via structural and conformational changes of membrane lipids and proteins, promote conditions for inner/outer membrane permeabilization, which may be followed by either opening of pores or a rupture of the outer mitochondrial membrane.
Tipo: | Info:eu-repo/semantics/article
Idioma: | Inglês
Identificador: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2007000800001
Editor: | Associação Brasileira de Divulgação Científica
Relação: | 10.1590/S0100-879X2006005000109
Formato: | text/html
Fonte: | Brazilian Journal of Medical and Biological Research  v.40 n.8 2007
Fonte: | info:eu-repo/semantics/openAccess