Wilson Zachary N, West Matt, English Alyssa M, Odorizzi Greg, Hughes Adam L
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO 80309.
bioRxiv. 2023 Jul 7:2023.07.07.548169. doi: 10.1101/2023.07.07.548169.
Preserving the health of the mitochondrial network is critical to cell viability and longevity. To do so, mitochondria employ several membrane remodeling mechanisms, including the formation of mitochondrial-derived vesicles (MDVs) and compartments (MDCs) to selectively remove portions of the organelle. In contrast to well-characterized MDVs, the distinguishing features of MDC formation and composition remain unclear. Here we used electron tomography to observe that MDCs form as large, multilamellar domains that generate concentric spherical compartments emerging from mitochondrial tubules at ER-mitochondria contact sites. Time-lapse fluorescence microscopy of MDC biogenesis revealed that mitochondrial membrane extensions repeatedly elongate, coalesce, and invaginate to form these compartments that encase multiple layers of membrane. As such, MDCs strongly sequester portions of the outer mitochondrial membrane, securing membrane cargo into a protected domain, while also enclosing cytosolic material within the MDC lumen. Collectively, our results provide a model for MDC formation and describe key features that distinguish MDCs from other previously identified mitochondrial structures and cargo-sorting domains.
维持线粒体网络的健康对于细胞的生存能力和寿命至关重要。为此，线粒体采用了多种膜重塑机制，包括形成线粒体衍生囊泡（MDV）和区室（MDC），以选择性地去除部分细胞器。与特征明确的MDV不同，MDC形成和组成的显著特征仍不清楚。在这里，我们使用电子断层扫描观察到，MDC形成为大的多层结构域，在内质网-线粒体接触位点从线粒体小管产生同心球形区室。MDC生物发生的延时荧光显微镜观察显示，线粒体膜延伸反复伸长、合并和内陷，形成包裹多层膜的这些区室。因此，MDC强烈隔离线粒体外膜的部分区域，将膜货物固定在一个受保护的区域，同时也将胞质物质包裹在MDC腔内。总的来说，我们的结果提供了一个MDC形成的模型，并描述了将MDC与其他先前鉴定的线粒体结构和货物分选结构域区分开来的关键特征。
