1. Academic Validation
  2. Mechanical instability generated by Myosin 19 contributes to mitochondria cristae architecture and OXPHOS

Mechanical instability generated by Myosin 19 contributes to mitochondria cristae architecture and OXPHOS

  • Nat Commun. 2022 May 13;13(1):2673. doi: 10.1038/s41467-022-30431-3.
Peng Shi  # 1 Xiaoyu Ren  # 1 Jie Meng  # 2 Chenlu Kang 1 Yihe Wu 1 Yingxue Rong 1 Shujuan Zhao 3 Zhaodi Jiang 4 Ling Liang 5 Wanzhong He 4 Yuxin Yin 1 Xiangdong Li 6 Yong Liu 7 Xiaoshuai Huang 8 Yujie Sun 9 Bo Li 10 Congying Wu 11 12
Affiliations

Affiliations

  • 1 Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
  • 2 Institute of Biomechanics and Medical Engineering, Applied Mechanics Laboratory, Department of Engineering Mechanics, Tsinghua University, Beijing, 100084, China.
  • 3 State Key Laboratory of Membrane Biology, Biomedical Pioneer Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, 100871, China.
  • 4 National Institute of Biological Sciences, Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, 102206, China.
  • 5 Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
  • 6 Group of Cell Motility and Muscle Contraction, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
  • 7 Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China. [email protected].
  • 8 Biomedical Engineering Department, Peking University, Beijing, 100191, China. [email protected].
  • 9 State Key Laboratory of Membrane Biology, Biomedical Pioneer Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, 100871, China. [email protected].
  • 10 Institute of Biomechanics and Medical Engineering, Applied Mechanics Laboratory, Department of Engineering Mechanics, Tsinghua University, Beijing, 100084, China. [email protected].
  • 11 Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. [email protected].
  • 12 International Cancer Institute, Peking University, Beijing, 100191, China. [email protected].
  • # Contributed equally.
Abstract

The folded mitochondria inner membrane-cristae is the structural foundation for oxidative phosphorylation (OXPHOS) and energy production. By mechanically simulating mitochondria morphogenesis, we speculate that efficient sculpting of the cristae is organelle non-autonomous. It has long been inferred that folding requires buckling in living systems. However, the tethering force for cristae formation and regulation has not been identified. Combining electron tomography, proteomics strategies, super resolution live cell imaging and mathematical modeling, we reveal that the mitochondria localized actin motor-myosin 19 (Myo19) is critical for maintaining cristae structure, by associating with the SAM-MICOS super complex. We discover that depletion of Myo19 or disruption of its motor activity leads to altered mitochondria membrane potential and decreased OXPHOS. We propose that Myo19 may act as a mechanical tether for effective ridging of the mitochondria cristae, thus sustaining the energy homeostasis essential for various cellular functions.

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