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The 40S ribosomal subunit recycling complex modulates mitochondrial dynamics and endoplasmic reticulum - mitochondria tethering at mitochondrial fission/fusion hotspots

Author

Listed:
  • Foozhan Tahmasebinia

    (Southern Methodist University)

  • Yinglu Tang

    (Southern Methodist University)

  • Rushi Tang

    (National University of Singapore)

  • Yi Zhang

    (Southern Methodist University)

  • Will Bonderer

    (Southern Methodist University)

  • Maisa Oliveira

    (Southern Methodist University)

  • Bretton Laboret

    (Southern Methodist University)

  • Songjie Chen

    (Stanford University School of Medicine)

  • Ruiqi Jian

    (Stanford University School of Medicine)

  • Lihua Jiang

    (Stanford University School of Medicine)

  • Michael Snyder

    (Stanford University School of Medicine)

  • Chun-Hong Chen

    (NHRI)

  • Yawei Shen

    (Clemson University
    Clemson University)

  • Qing Liu

    (Clemson University
    Clemson University)

  • Boxiang Liu

    (National University of Singapore
    National University of Singapore
    National University of Singapore
    Yong Loo Lin School of Medicine, National University of Singapore)

  • Zhihao Wu

    (Southern Methodist University)

Abstract

The 40S ribosomal subunit recycling pathway is an integral link in the cellular quality control network, occurring after translational errors have been corrected by the ribosome-associated quality control (RQC) machinery. Despite our understanding of its role, the impact of translation quality control on cellular metabolism remains poorly understood. Here, we reveal a conserved role of the 40S ribosomal subunit recycling (USP10-G3BP1) complex in regulating mitochondrial dynamics and function. The complex binds to fission-fusion proteins located at mitochondrial hotspots, regulating the functional assembly of endoplasmic reticulum-mitochondria contact sites (ERMCSs). Furthermore, it alters the activity of mTORC1/2 pathways, suggesting a link between quality control and energy fluctuations. Effective communication is essential for resolving proteostasis-related stresses. Our study illustrates that the USP10-G3BP1 complex acts as a hub that interacts with various pathways to adapt to environmental stimuli promptly. It advances our molecular understanding of RQC regulation and helps explain the pathogenesis of human proteostasis and mitochondrial dysfunction diseases.

Suggested Citation

  • Foozhan Tahmasebinia & Yinglu Tang & Rushi Tang & Yi Zhang & Will Bonderer & Maisa Oliveira & Bretton Laboret & Songjie Chen & Ruiqi Jian & Lihua Jiang & Michael Snyder & Chun-Hong Chen & Yawei Shen &, 2025. "The 40S ribosomal subunit recycling complex modulates mitochondrial dynamics and endoplasmic reticulum - mitochondria tethering at mitochondrial fission/fusion hotspots," Nature Communications, Nature, vol. 16(1), pages 1-24, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56346-3
    DOI: 10.1038/s41467-025-56346-3
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