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  3. Mitocytosis, a migrasome-mediated mitochondrial quality-control process

Mitocytosis, a migrasome-mediated mitochondrial quality-control process

  • Cell. 2021 May 27;184(11):2896-2910.e13. doi: 10.1016/j.cell.2021.04.027.
Haifeng Jiao 1,  Dong Jiang 1,  Xiaoyu Hu 1,  Wanqing Du 1,  Liangliang Ji 2,  Yuzhuo Yang 2,  Xiaopeng Li 1,  Takami Sho 1,  Xuan Wang 1,  Ying Li 1,  Yu-Ting Wu 3,  Yau-Huei Wei 3,  Xiaoyu Hu 2,  Li Yu 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Centre for Life Sciences, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, Beijing 100084, China.
  • 2 Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China.
  • 3 Center for Mitochondrial Medicine and Free Radical Research, Changhua Christian Hospital, Changhua City, Taiwan 50046.
  • 4 State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Centre for Life Sciences, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: liyulab@mail.tsinghua.edu.cn.
PMID: 34048705 DOI: 10.1016/j.cell.2021.04.027
Abstract

Damaged mitochondria need to be cleared to maintain the quality of the mitochondrial pool. Here, we report mitocytosis, a migrasome-mediated mitochondrial quality-control process. We found that, upon exposure to mild mitochondrial stresses, damaged mitochondria are transported into migrasomes and subsequently disposed of from migrating cells. Mechanistically, mitocytosis requires positioning of damaged mitochondria at the cell periphery, which occurs because damaged mitochondria avoid binding to inward motor proteins. Functionally, mitocytosis plays an important role in maintaining mitochondrial quality. Enhanced mitocytosis protects cells from mitochondrial stressor-induced loss of mitochondrial membrane potential (MMP) and mitochondrial respiration; conversely, blocking mitocytosis causes loss of MMP and mitochondrial respiration under normal conditions. Physiologically, we demonstrate that mitocytosis is required for maintaining MMP and viability in neutrophils in vivo. We propose that mitocytosis is an important mitochondrial quality-control process in migrating cells, which couples mitochondrial homeostasis with cell migration.

Keywords

migrasome; mitochondrial quality control; mitochondrion; mitocytosis; mitosome.

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