中国科学院生物物理研究所王晓晨等研究人员合作发现，HEAT重复蛋白HPO-27是一种溶酶体分裂因子。相关论文于2024年3月27日在线发表在《自然》杂志上。

研究人员发现HPO-27（一种保守的HEAT重复蛋白）是秀丽隐杆线虫溶酶体的分裂因子。HPO-27的缺失会影响溶酶体的分裂，导致管状网络过度扩张并最终崩溃。HPO-27及其人类同源物MROH1被RAB-7募集到溶酶体，并在分裂位点富集。

超分辨率成像、阴性染色电镜和体外重组实验显示，HPO-27和MROH1分别在线虫和哺乳动物细胞中自我组装，介导溶酶体小管的收缩和分裂，并在体外组装成断裂的支撑膜管。HPO-27的缺失会影响溶酶体的形态、完整性和降解活性，从而损害动物的发育和寿命。因此，HPO-27和MROH1是维持溶酶体平衡和功能的自组装分裂因子。

据悉，溶酶体是降解和信号中心，对细胞的稳态、发育和衰老至关重要。为了满足细胞的各种需求，溶酶体通过不断的融合和分裂重塑其形态和功能。人们对分裂的分子基础知之甚少。

附：英文原文

Title: The HEAT repeat protein HPO-27 is a lysosome fission factor

Author: Li, Letao, Liu, Xilu, Yang, Shanshan, Li, Meijiao, Wu, Yanwei, Hu, Siqi, Wang, Wenjuan, Jiang, Amin, Zhang, Qianqian, Zhang, Junbing, Ma, Xiaoli, Hu, Junyan, Zhao, Qiaohong, Liu, Yubing, Li, Dong, Hu, Junjie, Yang, Chonglin, Feng, Wei, Wang, Xiaochen

Issue&Volume: 2024-03-27

Abstract: Lysosomes are degradation and signalling centres crucial for homeostasis, development and ageing1. To meet diverse cellular demands, lysosomes remodel their morphology and function through constant fusion and fission2,3. Little is known about the molecular basis of fission. Here we identify HPO-27, a conserved HEAT repeat protein, as a lysosome scission factor in Caenorhabditis elegans. Loss of HPO-27 impairs lysosome fission and leads to an excessive tubular network that ultimately collapses. HPO-27 and its human homologue MROH1 are recruited to lysosomes by RAB-7 and enriched at scission sites. Super-resolution imaging, negative-staining electron microscopy and in vitro reconstitution assays reveal that HPO-27 and MROH1 self-assemble to mediate the constriction and scission of lysosomal tubules in worms and mammalian cells, respectively, and assemble to sever supported membrane tubes in vitro. Loss of HPO-27 affects lysosomal morphology, integrity and degradation activity, which impairs animal development and longevity. Thus, HPO-27 and MROH1 act as self-assembling scission factors to maintain lysosomal homeostasis and function.

DOI: 10.1038/s41586-024-07249-8

Source: https://www.nature.com/articles/s41586-024-07249-8