Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT.
Department of Biochemistry, University of Oxford, Oxford, UK.
J Cell Biol. 2020 Dec 7;219(12). doi: 10.1083/jcb.202002144.
Mitochondria are dynamic organelles with essential roles in signaling and metabolism. We recently identified a cellular structure called the mitochondrial-derived compartment (MDC) that is generated from mitochondria in response to amino acid overabundance stress. How cells form MDCs is unclear. Here, we show that MDCs are dynamic structures that form and stably persist at sites of contact between the ER and mitochondria. MDC biogenesis requires the ER-mitochondria encounter structure (ERMES) and the conserved GTPase Gem1, factors previously implicated in lipid exchange and membrane tethering at ER-mitochondria contacts. Interestingly, common genetic suppressors of abnormalities displayed by ERMES mutants exhibit distinct abilities to rescue MDC formation in ERMES-depleted strains and are incapable of rescuing MDC formation in cells lacking Gem1. Thus, the function of ERMES and Gem1 in MDC biogenesis may extend beyond their conventional role in maintaining mitochondrial phospholipid homeostasis. Overall, this study identifies an important function for ER-mitochondria contacts in the biogenesis of MDCs.
线粒体是具有重要信号和代谢功能的动态细胞器。我们最近发现了一种称为线粒体衍生区室（MDC）的细胞结构，它是在氨基酸过剩应激下从线粒体产生的。细胞如何形成 MDC 尚不清楚。在这里，我们表明 MDC 是动态结构，在 ER 和线粒体之间接触部位形成并稳定存在。MDC 的生物发生需要 ER-线粒体遭遇结构（ERMES）和保守的 GTPase Gem1，这两个因素先前被认为参与 ER-线粒体接触处的脂质交换和膜连接。有趣的是，ERMES 突变体显示的异常的常见遗传抑制剂表现出不同的能力，可以挽救 ERMES 耗尽菌株中 MDC 的形成，而不能挽救缺乏 Gem1 的细胞中 MDC 的形成。因此，ERMES 和 Gem1 在 MDC 生物发生中的功能可能超出了它们在维持线粒体磷脂稳态中的传统作用。总的来说，这项研究确定了 ER-线粒体接触在 MDC 生物发生中的重要作用。
