Proapoptotic Bid binds to monolysocardiolipin, a new molecular connection between mitochondrial membranes and cell death

Mauro Degli Esposti, I. M. Cristea, S. J. Gaskell, Y. Nakao, C. Dive

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

Recent evidence indicates that the mitochondrial lipid cardiolipin may be instrumental in the proapoptotic action of Bcl-2 family proteins on mitochondrial membranes, leading to the release of apoptogenic factors. However, contrasting evidence indicates that progressive loss of cardiolipin occurs during apoptosis. Here we show that Bid, a crucial proapoptotic protein that integrates the action of other Bcl-2 family members, exhibits discrete specificity for metabolites of cardiolipin, especially monolysocardiolipin (MCL). MCL, normally present in the remodelling of mitochondrial lipids, progressively increases in mitochondria during Fas-mediated apoptosis as a by-product of cardiolipin degradation, and also enhances Bid binding to membranes. MCL may thus play a crucial role in connecting lipid metabolism, relocation of Bid to mitochondria and integrated action of Bcl-2 proteins on mitochondrial membranes. We propose that Bid interaction with MCL 'primes' the mitochondrial outer membrane via segregation of lipid domains, facilitating membrane discontinuity and leakage of apoptogenic factors.

Original languageEnglish (US)
Pages (from-to)1300-1309
Number of pages10
JournalCell Death and Differentiation
Volume10
Issue number12
DOIs
StatePublished - Dec 1 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Keywords

  • Apoptosis
  • Bid
  • Cardiolipin
  • Mitochondria

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