Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
Biochemistry/Developmental Biology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
J Cell Biol. 2019 Jan 7;218(1):97-111. doi: 10.1083/jcb.201806191. Epub 2018 Nov 7.
Mitochondrial function is closely linked to its dynamic membrane ultrastructure. The mitochondrial inner membrane (MIM) can form extensive membrane invaginations known as cristae, which contain the respiratory chain and ATP synthase for oxidative phosphorylation. The molecular mechanisms regulating mitochondrial ultrastructure remain poorly understood. The Bin-Amphiphysin-Rvs (BAR) domain proteins are central regulators of diverse cellular processes related to membrane remodeling and dynamics. Whether BAR domain proteins are involved in sculpting membranes in specific submitochondrial compartments is largely unknown. In this study, we report FAM92A1 as a novel BAR domain protein localizes to the matrix side of the MIM. Loss of FAM92A1 caused a severe disruption to mitochondrial morphology and ultrastructure, impairing organelle bioenergetics. Furthermore, FAM92A1 displayed a membrane-remodeling activity in vitro, inducing a high degree of membrane curvature. Collectively, our findings uncover a role for a BAR domain protein as a critical organizer of the mitochondrial ultrastructure that is indispensable for mitochondrial function.
线粒体功能与其动态膜超微结构密切相关。线粒体的内（MIM）膜可以形成称为嵴的广泛膜内陷，其中包含呼吸链和 ATP 合酶进行氧化磷酸化。调节线粒体超微结构的分子机制仍知之甚少。Bin-Amphiphysin-Rvs（BAR）结构域蛋白是与膜重塑和动力学相关的多种细胞过程的核心调节剂。BAR 结构域蛋白是否参与塑造特定亚线粒体隔室中的膜在很大程度上尚不清楚。在这项研究中，我们报告 FAM92A1 是一种新型的 BAR 结构域蛋白，定位于 MIM 的基质侧。FAM92A1 的缺失导致线粒体形态和超微结构严重破坏，损害了细胞器的生物能量。此外，FAM92A1 在体外显示出膜重塑活性，诱导高度的膜曲率。总之，我们的研究结果揭示了 BAR 结构域蛋白作为线粒体超微结构的关键组织者的作用，对于线粒体功能是必不可少的。
