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

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143 Scopus citations

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 1 2004

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Kim, T. H., Zhao, Y., Ding, W. X., Shin, J. N., He, X., Seo, Y. W., Chen, J., Rabinowich, H., Amoscato, A. A., & Yin, X. M. (2004). Bid-cardiolipin interaction at mitochondrial contact site contributes to mitochondrial cristae reorganization and cytochrome c release. Molecular Biology of the Cell, 15(7), 3061-3072. https://doi.org/10.1091/mbc.E03-12-0864