Endoplasmic reticulum-specific BH3-only protein BNIP1 induces mitochondrial fragmentation in a Bcl-2- and Drp1-dependent manner |
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Authors: | Ryu Seung-Wook Choi Kyungsun Yoon Jonghee Kim Sunchang Choi Chulhee |
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Affiliation: | Department of Bio and Brain Engineering, KAIST, Daejeon, Korea. ryus@kaist.ac.kr |
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Abstract: | Bcl-2/adenovirus E1B 19-kDa interacting protein 1 (BNIP1), which is predominantly localized to the endoplasmic reticulum (ER), is a pro-apoptotic Bcl-2 homology domain 3 (BH3)-only protein. Here, we show that the expression of BNIP1 induced not only a highly interconnected ER network but also mitochondrial fragmentation in a BH3 domain-dependent manner. Functional analysis demonstrated that BNIP1 expression increased dynamin-related protein 1 (Drp1) expression followed by the mitochondrial translocation of Drp1 and subsequent mitochondrial fission. Both BNIP1-induced mitochondrial fission and the translocation of Drp1 were abrogated by Bcl-2 overexpression. These results collectively indicate that ER-specific BNIP1 plays an important role in mitochondrial dynamics by modulating the mitochondrial fission protein Drp1 in a BH3 domain-dependent fashion. |
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