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

Tae Hyoung Kim, Yongge Zhao, Wen Xing Ding, Jin Na Shin, Xi He, Young Woo Seo, Jun Chen, Hannah Rabinowich, Andrew A. Amoscato, Xiao-Ming Yin

Research output: Contribution to journalArticle

141 Citations (Scopus)

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 (α4-α6), but not the BH3 domain, and the binding could not be inhibited by the antideath molecule Bcl-xL. 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-xL. 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.

Original languageEnglish (US)
Pages (from-to)3061-3072
Number of pages12
JournalMolecular Biology of the Cell
Volume15
Issue number7
DOIs
StatePublished - Jul 2004
Externally publishedYes

Fingerprint

Cardiolipins
Cytochromes c
Mitochondria
Acridine Orange
Mitochondrial Membranes
Mass Spectrometry
Phospholipids
Coloring Agents
Apoptosis
Mutation
Membranes
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Bid-cardiolipin interaction at mitochondrial contact site contributes to mitochondrial cristae reorganization and cytochrome c release. / Kim, Tae Hyoung; Zhao, Yongge; Ding, Wen Xing; Shin, Jin Na; He, Xi; Seo, Young Woo; Chen, Jun; Rabinowich, Hannah; Amoscato, Andrew A.; Yin, Xiao-Ming.

In: Molecular Biology of the Cell, Vol. 15, No. 7, 07.2004, p. 3061-3072.

Research output: Contribution to journalArticle

Kim, Tae Hyoung ; Zhao, Yongge ; Ding, Wen Xing ; Shin, Jin Na ; He, Xi ; Seo, Young Woo ; Chen, Jun ; Rabinowich, Hannah ; Amoscato, Andrew A. ; Yin, Xiao-Ming. / Bid-cardiolipin interaction at mitochondrial contact site contributes to mitochondrial cristae reorganization and cytochrome c release. In: Molecular Biology of the Cell. 2004 ; Vol. 15, No. 7. pp. 3061-3072.
@article{5b94b7ad37ff4260a760eae91813f7b8,
title = "Bid-cardiolipin interaction at mitochondrial contact site contributes to mitochondrial cristae reorganization and cytochrome c release",
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 (α4-α6), but not the BH3 domain, and the binding could not be inhibited by the antideath molecule Bcl-xL. 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-xL. 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.",
author = "Kim, {Tae Hyoung} and Yongge Zhao and Ding, {Wen Xing} and Shin, {Jin Na} and Xi He and Seo, {Young Woo} and Jun Chen and Hannah Rabinowich and Amoscato, {Andrew A.} and Xiao-Ming Yin",
year = "2004",
month = "7",
doi = "10.1091/mbc.E03-12-0864",
language = "English (US)",
volume = "15",
pages = "3061--3072",
journal = "Molecular Biology of the Cell",
issn = "1059-1524",
publisher = "American Society for Cell Biology",
number = "7",

}

TY - JOUR

T1 - Bid-cardiolipin interaction at mitochondrial contact site contributes to mitochondrial cristae reorganization and cytochrome c release

AU - Kim, Tae Hyoung

AU - Zhao, Yongge

AU - Ding, Wen Xing

AU - Shin, Jin Na

AU - He, Xi

AU - Seo, Young Woo

AU - Chen, Jun

AU - Rabinowich, Hannah

AU - Amoscato, Andrew A.

AU - Yin, Xiao-Ming

PY - 2004/7

Y1 - 2004/7

N2 - 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 (α4-α6), but not the BH3 domain, and the binding could not be inhibited by the antideath molecule Bcl-xL. 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-xL. 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.

AB - 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 (α4-α6), but not the BH3 domain, and the binding could not be inhibited by the antideath molecule Bcl-xL. 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-xL. 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.

UR - http://www.scopus.com/inward/record.url?scp=3042723249&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3042723249&partnerID=8YFLogxK

U2 - 10.1091/mbc.E03-12-0864

DO - 10.1091/mbc.E03-12-0864

M3 - Article

VL - 15

SP - 3061

EP - 3072

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 7

ER -