Force- induced tail- autotomy mitochondrial fission and biogenesis of matrixexcluded mitochondrial- derived vesicles for quality control

• 成果类型: Article
• 署名作者: Liu, Xiaoying; Xu, Linyu; Song, Yutong; Zhao, Zhihao; Li, Xinyu; Wong, Cheuk - Yiu; Chen, Rong; Feng, Jianxiong; Gou, Yitao; Qi, Yajing; Chow, Hei-Man; Yao, Shuhuai; Wang, Yi; Gao, Song; Liu, Xingguo; Duan, Liting
• 署名单位: Chinese University of Hong Kong; Hong Kong University of Science & Technology; Sun Yat Sen University; State Key Lab Oncology South China; Chinese University of Hong Kong; Chinese University of Hong Kong; Chinese University of Hong Kong; Chinese University of Hong Kong; Hong Kong University of Science & Technology; Chinese Academy of Sciences; Guangzhou Institute of Biomedicine & Health, CAS; Guangzhou Medical University; Chinese Academy of Sciences
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14931
• DOI: 10.1073/pnas.2217019121
• 发表日期: 2024-03-25
• 关键词: optogenetic control; tether formation; mechanisms; transport; organelle; deformation; degradation; peroxisomes; RECRUITMENT; mitophagy

摘要

Mitochondria constantly fuse and divide for mitochondrial inheritance and functions. Here, we identified a distinct type of naturally occurring fission, tail- autotomy fission, wherein a tail - like thin tubule protrudes from the mitochondrial body and disconnects, resembling autotomy. Next, utilizing an optogenetic mitochondria- specific mechanostimulator, we revealed that mechanical tensile force drives tail- autotomy fission. This force- induced fission involves DRP1/MFF and endoplasmic reticulum tubule wrapping. It redistributes mitochondrial DNA, producing mitochondrial fragments with or without mitochondrial DNA for different fates. Moreover, tensile force can decouple outer and inner mitochondrial membranes, pulling out matrix- excluded tubule segments. Subsequent tail- autotomy fission separates the matrix- excluded tubule segments into matrix- excluded mitochondrial- derived vesicles (MDVs) which recruit Parkin and LC3B, indicating the unique role of tail- autotomy fission in segregating only outer membrane components for mitophagy. Sustained force promotes fission and MDV biogenesis more effectively than transient one. Our results uncover a mechanistically and functionally distinct type of fission and unveil the role of tensile forces in modulating fission and MDV biogenesis for quality control, underscoring the heterogeneity of fission and mechanoregulation of mitochondrial dynamics.