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Title: Opa1-mediated cristae opening is Bax/Bak and BH3 dependent, required for apoptosis, and independent of Bak oligomerization.

Authors: Yamaguchi, Ryuji; Lartigue, Lydia; Perkins, Guy; Scott, Ray T; Dixit, Amruta; Kushnareva, Yulia; Kuwana, Tomomi; Ellisman, Mark H; Newmeyer, Donald D

Published In Mol Cell, (2008 Aug 22)

Abstract: Controversy surrounds the role and mechanism of mitochondrial cristae remodeling in apoptosis. Here we show that the proapoptotic BH3-only proteins Bid and Bim induced full cytochrome c release but only a subtle alteration of crista junctions, which involved the disassembly of Opa1 complexes. Both mitochondrial outer membrane permeabilization (MOMP) and crista junction opening (CJO) were caspase independent and required a functional BH3 domain and Bax/Bak. However, MOMP and CJO were experimentally separable. Pharmacological blockade of MOMP did not prevent Opa1 disassembly and CJO; moreover, expression of a disassembly-resistant mutant Opa1 (Q297V) blocked cytochrome c release and apoptosis but not Bax activation. Thus, apoptosis requires a subtle form of Opa1-dependent crista remodeling that is induced by BH3-only proteins and Bax/Bak but independent of MOMP.

PubMed ID: 18691924 Exiting the NIEHS site

MeSH Terms: Animals; Apoptosis Regulatory Proteins/metabolism*; Apoptosis*/drug effects; BH3 Interacting Domain Death Agonist Protein/metabolism*; Bcl-2-Like Protein 11; Cells, Cultured; Cytochromes c/metabolism; GTP Phosphohydrolases/metabolism*; Humans; Leupeptins/pharmacology; Membrane Proteins/metabolism*; Mice; Mitochondria, Liver/drug effects; Mitochondria, Liver/metabolism*; Mitochondria, Liver/ultrastructure; Mitochondrial Membranes/drug effects; Mitochondrial Membranes/ultrastructure; Mutant Proteins/metabolism; Peptides/pharmacology; Permeability/drug effects; Protein Structure, Quaternary; Proto-Oncogene Proteins/metabolism*; bcl-2 Homologous Antagonist-Killer Protein/chemistry; bcl-2 Homologous Antagonist-Killer Protein/metabolism*; bcl-2-Associated X Protein/metabolism*

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