Bcl-2 family proteins, as central players of the apoptotic program, participate in regulation of the mitochondrial network. Here, a quantitative live-cell fluorescence resonance energy transfer (FRET) two-hybrid assay was used to confirm the homo-/hetero-oligomerization of mitofusins 2 and 1 (MFN2 and MFN1), and also demonstrate the binding of MFN2 to MFN1 with 1:1 stoichiometry. A FRET two-hybrid assay for living cells co-expressing CFP-labeled Bcl-XL (an anti-apoptotic Bcl-2 family protein encoded by BCL2L1) and YFP-labeled MFN2 or MFN1 demonstrated the binding of MFN2 or MFN1 to Bcl-XL with 1:1 stoichiometry. Neither MFN2 nor MFN1 bound with monomeric Bax in healthy cells, but both MFN2 and MFN1 bind to punctate Bax (pro-apoptotic Bcl-2 family protein) during apoptosis. Oligomerized Bak (also known as BAK1; a pro-apoptotic Bcl-2 family protein) only associated with MFN1 but not MFN2. Moreover, co-expression of Bcl-XL with MFN2 or MFN1 had the same anti-apoptotic effect as the expression of Bcl-XL alone to staurosporine-induced apoptosis, indicating the Bcl-XL has its full anti-apoptotic ability when complexed with MFN2 or MFN1. However, knockdown of MFN2 but not MFN1 reduced mitochondrial aggregation induced by overexpression of Bcl-XL, indicating that MFN2 but not MFN1 mediates Bcl-XL-induced mitochondrial aggregation.

Bcl-2 家族蛋白作为细胞凋亡程序的核心参与者，参与线粒体网络的调节。在此，使用定量活细胞荧光共振能量转移 (FRET) 双杂交测定来确认线粒体融合蛋白 2 和 1（MFN2 和 MFN1）的同源/异源寡聚化，并证明 MFN2 与 MFN1 的结合1:1 化学计量。对共表达 CFP 标记的 Bcl-XL（一种由BCL2L1编码的抗凋亡 Bcl-2 家族蛋白）和 YFP 标记的 MFN2 或 MFN1 的活细胞进行 FRET 双杂交测定，证明 MFN2 或 MFN1 与 Bcl-XL 的结合化学计量比为 1:1。在健康细胞中，MFN2 和 MFN1 均不与单体 Bax 结合，但在细胞凋亡过程中，MFN2 和 MFN1 均不与点状 Bax（促凋亡 Bcl-2 家族蛋白）结合。寡聚化 Bak（也称为 BAK1；一种促凋亡 Bcl-2 家族蛋白）仅与 MFN1 相关，但与 MFN2 无关。此外，Bcl-XL与MFN2或MFN1共表达对星形孢菌素诱导的细胞凋亡具有与单独表达Bcl-XL相同的抗凋亡作用，表明Bcl-XL与MFN2复合时具有完全的抗凋亡能力或最惠国待遇1。然而，敲低 MFN2 而不是 MFN1 会减少 Bcl-XL 过表达诱导的线粒体聚集，表明 MFN2 而不是 MFN1 介导 Bcl-XL 诱导的线粒体聚集。