Department of Molecular Biology, Massachusetts General Hospital, Boston Massachusetts, USA; Department of Genetics, Harvard Medical School, Boston Massachusetts, USA.
Department of Molecular Biology, Massachusetts General Hospital, Boston Massachusetts, USA.
J Biol Chem. 2024 Oct;300(10):107740. doi: 10.1016/j.jbc.2024.107740. Epub 2024 Aug 31.
Mitochondrial fusion requires the sequential merger of four bilayers to two. The outer-membrane solute carrier family 25 member (SLC25A46) interacts with both the outer and inner membrane dynamin family GTPases mitofusin 1/2 and optic atrophy 1 (Opa1). While SLC25A46 levels are known to affect mitochondrial morphology, how SLC25A46 interacts with mitofusin 1/2 and Opa1 to regulate membrane fusion is not understood. In this study, we use crosslinking mass spectrometry and AlphaFold 2 modeling to identify interfaces mediating an SLC25A46 interaction with Opa1 and Mfn2. We reveal that the bundle signaling element of Opa1 interacts with SLC25A46, and present evidence of an Mfn2 interaction involving the SLC25A46 cytosolic face. We validate these newly identified interaction interfaces and show that they play a role in mitochondrial network maintenance.
线粒体融合需要四个双层膜依次融合为两个。溶质载体家族 25 成员 46（SLC25A46）与外膜和内膜动力蛋白家族 GTP 酶（融合蛋白 1/2 和视神经萎缩蛋白 1（Opa1）相互作用。虽然已知 SLC25A46 的水平会影响线粒体形态，但 SLC25A46 如何与融合蛋白 1/2 和 Opa1 相互作用以调节膜融合尚不清楚。在这项研究中，我们使用交联质谱和 AlphaFold 2 建模来识别介导 SLC25A46 与 Opa1 和 Mfn2 相互作用的界面。我们揭示了 Opa1 的束状信号元件与 SLC25A46 相互作用，并提供了涉及 SLC25A46 胞质面的 Mfn2 相互作用的证据。我们验证了这些新鉴定的相互作用界面，并表明它们在维持线粒体网络中发挥作用。
