Cardiolipin provides specificity for targeting of tBid to mitochondria

Michael Lutter, Min Fang, Xu Luo, Masahiro Nishijima, Xiao Song Xie, Xiaodong Wang

Research output: Contribution to journalArticle

372 Citations (Scopus)

Abstract

Recent evidence supports the theory that mitochondrial homeostasis is the key regulatory step in apoptosis through the actions of members of the Bcl-2 family. Pro-apoptotic members of the family, such as Bax, Bad and Bid, can induce the loss of outer-membrane integrity with subsequent redistribution of pro-apoptotic proteins such as cytochrome c that are normally located in the intermembrane spaces of mitochondria. The anti-apoptotic members of the family, such as Bcl-2 and Bcl-X(L), protect the integrity of the mitochondrion and prevent the release of death-inducing factors. Bid normally exists in an inactive state in the cytosol, but after cleavage by caspase 8, the carboxy-terminal portion (tBid) moves from cytosol to mitochondria, where it induces release of cytochrome c. Here we address the question of what mediates specific targeting of tBid to the mitochondria. We provide evidence that cardiolipin, which is present in mitochondrial membranes, mediates the targeting of tBid to mitochondria through a previously unkown three-helix domain in tBid. These findings implicate cardiolipin in the pathway for cytochrome c release.

Original languageEnglish (US)
Pages (from-to)754-756
Number of pages3
JournalNature Cell Biology
Volume2
Issue number10
DOIs
StatePublished - Oct 1 2000

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Cardiolipins
Mitochondria
Cytochromes c
Cytosol
Apoptosis Regulatory Proteins
Caspase 8
Mitochondrial Membranes
Homeostasis
Apoptosis
Membranes

ASJC Scopus subject areas

  • Cell Biology

Cite this

Lutter, M., Fang, M., Luo, X., Nishijima, M., Xie, X. S., & Wang, X. (2000). Cardiolipin provides specificity for targeting of tBid to mitochondria. Nature Cell Biology, 2(10), 754-756. https://doi.org/10.1038/35036395

Cardiolipin provides specificity for targeting of tBid to mitochondria. / Lutter, Michael; Fang, Min; Luo, Xu; Nishijima, Masahiro; Xie, Xiao Song; Wang, Xiaodong.

In: Nature Cell Biology, Vol. 2, No. 10, 01.10.2000, p. 754-756.

Research output: Contribution to journalArticle

Lutter, M, Fang, M, Luo, X, Nishijima, M, Xie, XS & Wang, X 2000, 'Cardiolipin provides specificity for targeting of tBid to mitochondria', Nature Cell Biology, vol. 2, no. 10, pp. 754-756. https://doi.org/10.1038/35036395
Lutter, Michael ; Fang, Min ; Luo, Xu ; Nishijima, Masahiro ; Xie, Xiao Song ; Wang, Xiaodong. / Cardiolipin provides specificity for targeting of tBid to mitochondria. In: Nature Cell Biology. 2000 ; Vol. 2, No. 10. pp. 754-756.
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