小柯机器人

近日，瑞士洛桑联邦理工学院Suliana Manley、Tatjana Kleele等研究人员合作发现，不同的分裂特征能够预测线粒体降解或生物发生。这一研究成果于2021年5月5日在线发表在国际学术期刊《自然》上。

据研究人员介绍，线粒体分裂是一个高度调控的过程，一旦被破坏，就会改变新陈代谢、增殖和凋亡。其失调与神经退行性变、心血管疾病和癌症有关。分裂机器的关键组成部分包括内质网和肌动蛋白，它们在动力蛋白相关蛋白1（DRP1）通过衔接蛋白结合到线粒体外膜上驱动分裂之前开始收缩。在线粒体的生命周期中，分裂既可以使新的线粒体发生生物，又可以通过线粒体清除功能异常的线粒体。当前的分裂调节模型无法解释这些双重命运是如何决定的。然而，发现命运决定因素是一项挑战，因为分裂是不可预测的，且线粒体形态是异质的，其超微结构特征低于衍射极限。

研究人员使用活细胞结构照明显微镜来捕获了线粒体动态。通过分析非洲绿猴Cos-7细胞和小鼠心肌细胞中的数百个分裂过程，研究人员发现了两种在功能和机制上均不同的分裂类型。外围的分裂使得受损的材料掉落到较小的线粒体中，从而进行线粒体吞噬，而中间区域的分裂则导致线粒体的增殖。两种类型均由DRP1介导，但内质网和肌动蛋白介导的预收缩以及衔接蛋白MFF仅控制中区的分裂。周围的分裂早于溶酶体接触，并受线粒体外膜蛋白FIS1调控。这些独特的分子机制解释了细胞如何独立调节分裂，从而导致独特的线粒体命运。 

附：英文原文

Title: Distinct fission signatures predict mitochondrial degradation or biogenesis

Author: Tatjana Kleele, Timo Rey, Julius Winter, Sofia Zaganelli, Dora Mahecic, Hlne Perreten Lambert, Francesco Paolo Ruberto, Mohamed Nemir, Timothy Wai, Thierry Pedrazzini, Suliana Manley

Issue&Volume: 2021-05-05

Abstract: Mitochondrial fission is a highly regulated process that, when disrupted, can alter metabolism, proliferation and apoptosis1,2,3. Dysregulation has been linked to neurodegeneration3,4, cardiovascular disease3 and cancer5. Key components of the fission machinery include the endoplasmic reticulum6 and actin7, which initiate constriction before dynamin-related protein 1 (DRP1)8 binds to the outer mitochondrial membrane via adaptor proteins9,10,11, to drive scission12. In the mitochondrial life cycle, fission enables both biogenesis of new mitochondria and clearance of dysfunctional mitochondria through mitophagy1,13. Current models of fission regulation cannot explain how those dual fates are decided. However, uncovering fate determinants is challenging, as fission is unpredictable, and mitochondrial morphology is heterogeneous, with ultrastructural features that are below the diffraction limit. Here, we used live-cell structured illumination microscopy to capture mitochondrial dynamics. By analysing hundreds of fissions in African green monkey Cos-7 cells and mouse cardiomyocytes, we discovered two functionally and mechanistically distinct types of fission. Division at the periphery enables damaged material to be shed into smaller mitochondria destined for mitophagy, whereas division at the midzone leads to the proliferation of mitochondria. Both types are mediated by DRP1, but endoplasmic reticulum- and actin-mediated pre-constriction and the adaptor MFF govern only midzone fission. Peripheral fission is preceded by lysosomal contact and is regulated by the mitochondrial outer membrane protein FIS1. These distinct molecular mechanisms explain how cells independently regulate fission, leading to distinct mitochondrial fates.

DOI: 10.1038/s41586-021-03510-6

Source: https://www.nature.com/articles/s41586-021-03510-6

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html