Mitofusin 2 but not mitofusin 1 mediates Bcl-XL-induced mitochondrial aggregation
- 1 January 2020
- journal article
- research article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 133 (20)
- https://doi.org/10.1242/jcs.245001
Abstract
Bcl-2 family proteins, as central players of apoptotic program, participate in the regulation of mitochondrial network. Here, quantitative live-cell Fluorescence Resonance Energy Transfer (FRET) two-hybrid assay was used to confirm the homo-/hetero-oligomerization of mitofusins (MFN2 and MFN1), and also demonstrate the binding of MFN2 to MFN1 with 1:1 stoichiometry. FRET two-hybrid assay for living cells co-expressing CFP-labeled Bcl-XL (anti-apoptotic Bcl-2 family protein) and YFP-labeled MFN2/MFN1 demonstrate the binding of MFN2/MFN1 to Bcl-XL with 1:1 stoichiometry. Neither MFN2 nor MFN1 bind with monomeric Bax in healthy cells, but both MFN2 and MFN1 combine with punctate Bax (pro-apoptotic Bcl-2 family protein) during apoptosis. Oligomerized Bak (pro-apoptotic Bcl-2 family protein) can only associates with MFN1 but not MFN2. Moreover, co-expression of Bcl-XL and MFN2/MFN1 exhibited the same anti-apoptotic ability as the expression of Bcl-XL alone to staurosporine-induced apoptosis, indicating the full anti-apoptotic ability of Bcl-XL complexed with MFN2 or MFN1. However, knockdown of MFN2 but not MFN1 reduced mitochondrial aggregation induced by overexpressed Bcl-XL, indicating that MFN2 but not MFN1 mediates Bcl-XL-induced mitochondrial aggregation.Keywords
Funding Information
- National Natural Science Foundation of China (61527825)
- Science and Technology Program of Guangzhou (2019050001)
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