西湖大学唐鸿云和北京大学黄小帅团队合作揭示，线粒体囊的产生是线粒体特异性外泌的一种形式，调节精子线粒体数量和生育能力。这一研究成果发表在2023年11月9日出版的国际学术期刊《自然—细胞生物学》上。

他们描述了线粒体囊的产生，这是一个以前未知的过程，通过称为“线粒体囊”的独特细胞外囊泡特异性地分泌线粒体。他们观察到，在雄性秀丽隐杆线虫的精子发育过程中，健康的线粒体通过有丝分裂从精子中输出，每个产生的有丝分裂细胞只含有一个线粒体。在有丝分裂发生中，质膜首先形成嵌入线粒体的外芽，然后芽迅速脱落，从而导致有丝分裂的产生。从机制上讲，睾丸中的细胞外蛋白酶信号触发精子形成丝分裂，这部分是由酪氨酸激酶SPE-8介导的。此外，丝分裂发生需要正常的微丝动力学，而肌凝蛋白VI可拮抗丝分裂的产生。

引人注目的是，他们的三维电子显微镜分析表明，在精子发育过程中，线粒体数量需要精确调节，这是由线粒体分裂发生介导的。抑制线粒体分裂会导致精子中线粒体的积累，这可能导致精子运动和生育缺陷。他们的研究结果表明，线粒体分裂是线粒体特异性外泌的一个先前未被描述的过程，这可能代表了线粒体数量控制机制的一个基本分支，以调节发育过程中的细胞功能。

据悉，线粒体输出到细胞外空间是一个基本的细胞过程，涉及多种生理活动。尽管一些研究已经阐明了受损线粒体的丢弃过程，但线粒体是如何输出的以及线粒体释放的功能在很大程度上仍然不清楚。

附：英文原文

Title: Mitopherogenesis, a form of mitochondria-specific ectocytosis, regulates sperm mitochondrial quantity and fertility

Author: Liu, Peng, Shi, Jing, Sheng, Danli, Lu, Wenqing, Guo, Jie, Gao, Lei, Wang, Xiaoqing, Wu, Shaofeng, Feng, Yanwen, Dong, Dashan, Huang, Xiaoshuai, Tang, Hongyun

Issue&Volume: 2023-11-09

Abstract: Mitochondrial export into the extracellular space is emerging as a fundamental cellular process implicated in diverse physiological activities. Although a few studies have shed light on the process of discarding damaged mitochondria, how mitochondria are exported and the functions of mitochondrial release remain largely unclear. Here we describe mitopherogenesis, a formerly unknown process that specifically secretes mitochondria through a unique extracellular vesicle termed a ‘mitopher’. We observed that during sperm development in male Caenorhabditis elegans, healthy mitochondria are exported out of the spermatids through mitopherogenesis and each of the generated mitophers harbours only one mitochondrion. In mitopherogenesis, the plasma membrane first forms mitochondrion-embedding outward buds, which then promptly bud off and thereby result in the generation of mitophers. Mechanistically, extracellular protease signalling in the testis triggers mitopher formation from spermatids, which is partially mediated by the tyrosine kinase SPE-8. Moreover, mitopherogenesis requires normal microfilament dynamics, whereas myosin VI antagonizes mitopher generation. Strikingly, our three-dimensional electron microscopy analyses indicate that mitochondrial quantity requires precise modulation during sperm development, which is critically mediated by mitopherogenesis. Inhibition of mitopherogenesis causes accumulation of mitochondria in sperm, which may lead to sperm motility and fertility defects. Our findings identify mitopherogenesis as a previously undescribed process for mitochondria-specific ectocytosis, which may represent a fundamental branch of mechanisms underlying mitochondrial quantity control to regulate cell functions during development. Liu et al. describe mitopherogenesis: the secretion of mitochondria in mitophers during sperm development in Caenorhabditis elegans, which is important to control the mitochondrial pool and ensure fertility.

DOI: 10.1038/s41556-023-01264-z

Source: https://www.nature.com/articles/s41556-023-01264-z