Journal
CANCER LETTERS
Volume 323, Issue 1, Pages 62-68Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2012.03.038
Keywords
Apoptosis; Bax; Mitochondria; Mitofusin; Mfn1; Mfn2; Outer mitochondrial membrane
Categories
Funding
- Ministry of Health & Welfare, Republic of Korea [A111025]
- National Research Foundation [NRF-2008-359-C00026]
- Korean Government
- Korea Health Promotion Institute [A111025] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2008-359-C00026] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
Mitochondrial fusion and fission are dynamically regulated during apoptotic cell death, and mitofusin (Mfn) and related proteins have been shown to be involved in apoptosis-associated changes in mitochondrial morphology and function. Here, we investigated the involvement of Mfn proteins in the conformational activation and mitochondrial translocation of Bax, a key molecule responsible for apoptosis-associated mitochondrial changes. When ectopically expressed, Mfn1 inhibited the amino-terminal activation, but not the mitochondrial translocation, of Bax during staurosporine-induced apoptosis; overexpression of Mfn2 had no effect. Overexpression of Mfn1 mutants carrying point mutations in the GTPase domain (Mfn1-1038T and Mfn1-T109A) did not inhibit the amino-terminal activation of Bax. Furthermore, staurosporine-induced amino-terminal activation of Bax was significantly delayed in Mfn1-shRNA transfected (Mfn1-depleted) HeLa cells compared to cells transfected with control shRNA. These results collectively suggest a role for Mfn1 in regulating the activation of Bax on the outer mitochondrial membrane in a GTPase-dependent manner. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available