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

研究成果: 雜誌貢獻文章同行評審

38 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)3952-3963
頁數12
期刊Molecular Biology of the Cell
17
發行號9
DOIs
出版狀態已發佈 - 9月 2006
對外發佈

ASJC Scopus subject areas

  • 細胞生物學
  • 遺傳學
  • 分子生物學

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