Mitofusin 1 inhibits an apoptosis-associated amino-terminal conformational change in Bax, but not its mitochondrial translocation, in a GTPase-dependent manner

作者：Ryu Seung Wook^*; Choi Kyungsun; Park Jong Hwan; Park Yeong Min; Kim Sunchang; Choi Chulhee

来源：Cancer Letters, 2012, 323(1): 62-68.

DOI：10.1016/j.canlet.2012.03.038

• Apoptosis
• Bax
• Mitochondria
• Mitofusin
• Mfn1
• Mfn2
• Outer mitochondrial membrane

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.

• 出版日期2012-10-1