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PMID: 15107464 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Bid-cardiolipin interaction at mitochondrial contact site contributes to mitochondrial cristae reorganization and cytochrome C release.

Molecular biology of the cell ·Vol. 15 ·No. 7 ·2004-07-00 ·Pages 3061-72

Kim TH, Zhao Y, Ding WX, Shin JN, He X, Seo YW, Chen J, Rabinowich H, Amoscato AA, Yin XM

Abstract

Release of cytochrome c from the mitochondrial intermembrane space is critical to apoptosis induced by a variety of death stimuli. Bid is a BH3-only prodeath Bcl-2 family protein that can potently activate this efflux. In the current study, we investigated the mitochondrial localization of Bid and its interactions with mitochondrial phospholipids, focusing on their relationships with Bid-induced cytochrome c release. We found that Bid binding to the mitochondria required only three of its eight helical structures (alpha4-alpha6), but not the BH3 domain, and the binding could not be inhibited by the antideath molecule Bcl-x(L). Membrane fractionations indicated that tBid bound to mitochondrial outer membranes at both contact and noncontact sites. Bid could interact with specific cardiolipin species on intact mitochondria as identified by mass spectrometry. Like the binding to the mitochondria, this interaction could not be blocked by the mutation in the BH3 domain or by Bcl-x(L.) However, a cardiolipin-specific dye, 10-N-nonyl acridine orange, could preferentially suppress Bid binding to the mitochondrial contact site and inhibit Bid-induced mitochondrial cristae reorganization and cytochrome c release. These findings thus suggest that interactions of Bid with mitochondrial cardiolipin at the contact site can contribute significantly to its functions.

MeSH Terms
Aminoacridines/pharmacology Animals BH3 Interacting Domain Death Agonist Protein Cardiolipins/analysis,metabolism Carrier Proteins/analysis,genetics,metabolism Cytochromes c/metabolism Membrane Proteins/analysis,metabolism Mice Mitochondria/immunology,metabolism,ultrastructure Protein Structure, Tertiary/genetics Protein Transport/drug effects Proto-Oncogene Proteins c-bcl-2/analysis,metabolism bcl-2 Homologous Antagonist-Killer Protein bcl-X Protein
Chemicals
Aminoacridines BH3 Interacting Domain Death Agonist Protein Bak1 protein, mouse Bcl2l1 protein, mouse Bid protein, mouse Cardiolipins Carrier Proteins Membrane Proteins Proto-Oncogene Proteins c-bcl-2 bcl-2 Homologous Antagonist-Killer Protein bcl-X Protein 10-N-nonylacridinium orange Cytochromes c
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Kim Tae-Hyoung
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Zhao Yongge
Ding Wen-Xing
Shin Jin Na
He Xi
Seo Young-Woo
Chen Jun
Rabinowich Hannah
Amoscato Andrew A
Yin Xiao-Ming
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
Published
2004-07-00
Epub
2004-00-23
Pages
3061-72
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC452564
Subset
IM
Grants
NCI NIH HHS · CA R01-83817 · United States
NINDS NIH HHS · NS R01-04252 · United States
PHS HHS · R01-92389 · United States
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