An internal EELD domain facilitates mitochondrial targeting of Mcl-1 via a Tom70-dependent pathway

Jiang-Hung Chou, Ru Shuo Lee, Hsin Fang Yang-Yen

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30 Citations (Scopus)

Abstract

Mcl-1 functions at an apical step in many regulatory programs that control cell death. Although the mitochondrion is one major subcellular organelle where Mcl-1 functions, the molecular mechanism by which Mcl-1 is targeted to mitochondria remains unclear. Here, we demonstrate that Mcl-1 is loosely associated with the outer membrane of mitochondria. Furthermore, we demonstrate that Mcl-1 interacts with the mitochondrial import receptor Tom70, and such interaction requires an internal domain of Mcl-1 that contains an EELD motif. A Tom70 antibody that blocks Mcl-1-Tom70 interaction blocks mitochondrial import of Mcl-1 in vitro. Furthermore, Mcl-1 is significantly less targeted to mitochondria in Tom70 knockdown than in the control cells. Similar targeting preference is also observed for the DM mutant of Mcl-1 whose mutation at the EELD motif markedly attenuates its Tom70 binding activity. Together, our results indicate that the internal EELD domain facilitates mitochondrial targeting of Mcl-1 via a Tom70-dependent pathway.

Original languageEnglish
Pages (from-to)3952-3963
Number of pages12
JournalMolecular Biology of the Cell
Volume17
Issue number9
DOIs
Publication statusPublished - Sep 2006
Externally publishedYes

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ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

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