Abstract:
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.
摘要:
保持线粒体网络的健康对于细胞活力和寿命至关重要。要做到这一点,线粒体采用几种膜重塑机制,包括线粒体来源的囊泡(MDV)和区室(MDC)的形成,以选择性地去除细胞器的部分。与特征明确的MDV相比,MDC形成和组成的区别特征仍不清楚。这里,我们使用电子层析成像来观察MDC的大小,在ER-线粒体接触部位产生从线粒体小管出现的同心球形区室的多层结构域。MDC生物发生的延时荧光显微镜显示,线粒体膜延伸反复拉长,合并,并内陷形成这些包裹多层膜的隔室。因此,MDC强烈隔离线粒体外膜的部分,将膜货物固定到受保护的域中,同时也将胞质材料封闭在MDC腔内。总的来说,我们的结果为MDC形成提供了一个模型,并描述了将MDC与其他先前鉴定的线粒体结构和货物分选域区分开的关键特征.