Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
J Cell Biol. 2023 Oct 2;222(10). doi: 10.1083/jcb.202303147. Epub 2023 Aug 4.
Mitochondria are highly dynamic double membrane-bound organelles that maintain their shape in part through fission and fusion. Mitochondrial fission is performed by a dynamin-related protein, Dnm1 (Drp1 in humans), that constricts and divides the mitochondria in a GTP hydrolysis-dependent manner. However, it is unclear whether factors inside mitochondria help coordinate the process and if Dnm1/Drp1 activity is sufficient to complete the fission of both mitochondrial membranes. Here, we identify an intermembrane space protein required for mitochondrial fission in yeast, which we propose to name Mdi1 (also named Atg44). Loss of Mdi1 causes mitochondrial hyperfusion due to defects in fission, but not the lack of Dnm1 recruitment to mitochondria. Mdi1 is conserved in fungal species, and its homologs contain an amphipathic α-helix, mutations of which disrupt mitochondrial morphology. One model is that Mdi1 distorts mitochondrial membranes to enable Dnm1 to robustly complete fission. Our work reveals that Dnm1 cannot efficiently divide mitochondria without the coordinated function of Mdi1 inside mitochondria.
线粒体是高度动态的双层膜细胞器，其形状部分通过分裂和融合来维持。线粒体的分裂是由一种与 dynamin 相关的蛋白（人类中的 Dnm1，也称为 Drp1）完成的，它通过 GTP 水解依赖性的方式收缩并分裂线粒体。然而，目前尚不清楚线粒体内部的因素是否有助于协调这个过程，以及 Dnm1/Drp1 的活性是否足以完成两个线粒体膜的分裂。在这里，我们鉴定了酵母中线粒体分裂所必需的一种内膜空间蛋白，我们将其命名为 Mdi1（也称为 Atg44）。由于分裂缺陷，Mdi1 的缺失会导致线粒体过度融合，但不会导致 Dnm1 招募到线粒体。Mdi1 在真菌物种中是保守的，其同源物包含一个两亲性α-螺旋，突变会破坏线粒体的形态。一种模型是，Mdi1 使线粒体膜变形，从而使 Dnm1 能够有效地完成分裂。我们的工作表明，没有 Mdi1 在线粒体内部的协调作用，Dnm1 就不能有效地分裂线粒体。
