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Metaxin is required for tumor necrosis factor‐induced cell death
Author(s) -
Wang Xiaofei,
Ono Koh,
Ouk Kim Sung,
Kravchenko Vladimir,
Lin ShengCai,
Han Jiahuai
Publication year - 2001
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1093/embo-reports/kve135
Subject(s) - programmed cell death , tumor necrosis factor alpha , biology , apoptosis , ectopic expression , microbiology and biotechnology , mitochondrion , necrosis , cell culture , mutant , gene , genetics , immunology
We used retrovirus insertion‐mediated random mutagenesis and tumor necrosis factor (TNF) selection to generate TNF‐resistant lines from L929 cells. The metaxin gene, which encodes a protein located on the outer membrane of mitochondria, was identified to be the gene disrupted in one of the resistant lines. The requirement of metaxin in TNF‐induced cell death of L929 was confirmed by the restoration of TNF sensitivity after ectopic reconstitution of metaxin expression. Analysis of the cell death induced by other stimuli revealed that metaxin deficiency‐mediated death resistance was selective to certain stimuli. Studies using deletion mutants of metaxin showed that mitochondrial association of metaxin is required for the function of metaxin. Over‐expression of truncated metaxin lacking the mitochondria anchoring sequence mimicked metaxin deficiency in wild‐type cells. Interfering with metaxin prevented TNF‐induced necrotic cell death in L929 cells and apoptosis in MCF‐7 cells. Our work has thus defined a novel component in the death pathway used by TNF and some other death stimuli.