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Highly conserved shifts in ubiquitin-proteasome system (UPS) activity drive mitochondrial remodeling during quiescence

Author

Listed:
  • Sibiao Yue

    (UT Southwestern Medical Center)

  • Lei Wang

    (UT Southwestern Medical Center)

  • George N. DeMartino

    (UT Southwestern Medical Center)

  • FangZhou Zhao

    (UT Southwestern Medical Center)

  • Yi Liu

    (UT Southwestern Medical Center)

  • Matthew H. Sieber

    (UT Southwestern Medical Center)

Abstract

Defects in cellular proteostasis and mitochondrial function drive many aspects of infertility, cancer, and other age-related diseases. All of these conditions rely on quiescent cells, such as oocytes and adult stem cells, that reduce their activity and remain dormant as part of their roles in tissue homeostasis, reproduction, and even cancer recurrence. Using a multi-organism approach, we show that dynamic shifts in the ubiquitin proteasome system drive mitochondrial remodeling during cellular quiescence. In contrast to the commonly held view that the ubiquitin-proteasome system (UPS) is primarily regulated by substrate ubiquitination, we find that increasing proteasome number and their recruitment to mitochondria support mitochondrial respiratory quiescence (MRQ). GSK3 triggers proteasome recruitment to the mitochondria by phosphorylating outer membrane proteins, such as VDAC, and suppressing mitochondrial fatty acid oxidation. This work defines a process that couples dynamic regulation of UPS activity to coordinated shifts in mitochondrial metabolism in fungi, Drosophila, and mammals during quiescence.

Suggested Citation

  • Sibiao Yue & Lei Wang & George N. DeMartino & FangZhou Zhao & Yi Liu & Matthew H. Sieber, 2022. "Highly conserved shifts in ubiquitin-proteasome system (UPS) activity drive mitochondrial remodeling during quiescence," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32206-2
    DOI: 10.1038/s41467-022-32206-2
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    References listed on IDEAS

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    1. Linhao Ruan & Chuankai Zhou & Erli Jin & Andrei Kucharavy & Ying Zhang & Zhihui Wen & Laurence Florens & Rong Li, 2017. "Cytosolic proteostasis through importing of misfolded proteins into mitochondria," Nature, Nature, vol. 543(7645), pages 443-446, March.
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    Cited by:

    1. Annabel Qi En Ng & Seow Neng Chan & Jun Wei Pek, 2024. "Nutrient-dependent regulation of a stable intron modulates germline mitochondrial quality control," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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