Institut de Biologie du Développement de Marseille-Luminy, CNRS UMR 6216/Aix-Marseille Universités, F-13288 Marseille, France.
EMBO Rep. 2011 Mar;12(3):223-30. doi: 10.1038/embor.2010.214. Epub 2011 Jan 28.
Mitochondria are highly dynamic organelles that can change in number and morphology during cell cycle, development or in response to extracellular stimuli. These morphological dynamics are controlled by a tight balance between two antagonistic pathways that promote fusion and fission. Genetic approaches have identified a cohort of conserved proteins that form the core of mitochondrial remodelling machineries. Mitofusins (MFNs) and OPA1 proteins are dynamin-related GTPases that are required for outer- and inner-mitochondrial membrane fusion respectively whereas dynamin-related protein 1 (DRP1) is the master regulator of mitochondrial fission. We demonstrate here that the Drosophila PMI gene and its human orthologue TMEM11 encode mitochondrial inner-membrane proteins that regulate mitochondrial morphogenesis. PMI-mutant cells contain a highly condensed mitochondrial network, suggesting that PMI has either a pro-fission or an anti-fusion function. Surprisingly, however, epistatic experiments indicate that PMI shapes the mitochondria through a mechanism that is independent of drp1 and mfn. This shows that mitochondrial networks can be shaped in higher eukaryotes by at least two separate pathways: one PMI-dependent and one DRP1/MFN-dependent.
线粒体是高度动态的细胞器，其数量和形态可在细胞周期、发育过程中或对外界刺激的反应中发生变化。这些形态动力学由两种拮抗途径之间的紧密平衡来控制，这两种途径分别促进融合和裂变。遗传方法已经鉴定出一群保守的蛋白质，它们构成了线粒体重塑机制的核心。线粒体融合蛋白（MFNs）和 OPA1 蛋白是动力相关 GTP 酶，分别是外膜和内膜融合所必需的，而动力相关蛋白 1（DRP1）是线粒体裂变的主要调节因子。我们在这里证明，果蝇 PMI 基因及其人类同源物 TMEM11 编码调节线粒体形态发生的线粒体内膜蛋白。PMI 突变细胞含有高度浓缩的线粒体网络，这表明 PMI 具有促分裂或抗融合功能。然而，令人惊讶的是，上位性实验表明，PMI 通过一种独立于 drp1 和 mfn 的机制来塑造线粒体。这表明线粒体网络可以通过至少两种独立的途径在高等真核生物中形成：一种依赖于 PMI，另一种依赖于 DRP1/MFN。
