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TUFM: a central regulator in mitochondrial quality control and beyond
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  • Review Article
  • Open access
  • Published: 28 March 2026

TUFM: a central regulator in mitochondrial quality control and beyond

  • Xuanyi Li1,
  • Liangjie Dong1,
  • Tian Xiao1,
  • Jiayi Chen2,
  • Hang Ye2,
  • Siyi Zhu2,
  • Fulin Chen1,2,3 &
  • …
  • Yuan Yu  ORCID: orcid.org/0000-0002-7123-669X1,2,3 

Cell Death Discovery , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Apoptosis
  • Energy metabolism
  • Immune evasion
  • Mitophagy
  • Tumour biomarkers

Abstract

Tu translation elongation factor, mitochondrial (TUFM) is a highly conserved, nuclear-encoded GTPase that is indispensable for mitochondrial protein synthesis. Beyond this canonical function, TUFM has emerged as a central regulator of mitochondrial quality control (MQC), orchestrating mitochondrial biogenesis, dynamics, and mitophagy through a location-dictates-function paradigm. Its subcellular localization and activity are precisely regulated by post-translational modifications, including phosphorylation, lactylation, ubiquitination, and acetylation, which collectively dictate its functional outputs in cellular homeostasis and stress responses. TUFM also serves as a critical interface in host-pathogen interactions, where viruses often hijack its pro-mitophagic function to evade mitochondrial antiviral signaling. Functioning as a cellular fate switch, the TUFM-MQC axis determines context-dependent pathological outcomes: its hyperactivation promotes cell growth and fuels oncogenesis, whereas its deficiency exacerbates cell death and contributes to neurodegeneration, inflammatory damage, and metabolic dysfunction. This review synthesizes current mechanistic insights into TUFM as a central MQC coordinator and delineates how its functional imbalance redirects cellular trajectories toward survival or death. Deciphering the regulatory logic and spatiotemporal dynamics of this pivotal hub offers promising avenues for developing targeted strategies to restore cellular homeostasis across a spectrum of diseases.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (31900330), the Natural Science Basic Research Plan in Shaanxi Province of China (2024JC-YBMS-182), and the Shaanxi Fundamental Science Research Project for Chemistry and Biology (23JHQ067). During the preparation of this work, the author(s) used DeepSeek-V3.1 in order to assist with language polishing and refinement. After using this tool, the author(s) reviewed and edited the content as needed and take full responsibility for the content of the published article. Figures were created with BioRender.com.

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Authors and Affiliations

  1. Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi’an, China

    Xuanyi Li, Liangjie Dong, Tian Xiao, Fulin Chen & Yuan Yu

  2. Laboratory of Tissue Engineering, College of Life Sciences, Northwest University, Xi’an, China

    Jiayi Chen, Hang Ye, Siyi Zhu, Fulin Chen & Yuan Yu

  3. Provincial Key Laboratory of Biotechnology of Shaanxi, Northwest University, Xi’an, China

    Fulin Chen & Yuan Yu

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  1. Xuanyi Li
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Contributions

Xuanyi Li: writing—original draft, writing—review & editing, investigation. Liangjie Dong: visualization, investigation. Tian Xiao: visualization, investigation. Jiayi Chen: conceptualization. Hang Ye: investigation. Siyi Zhu: project administration. Fulin Chen: supervision, conceptualization. Yuan Yu: writing—review & editing, funding acquisition, conceptualization.

Corresponding author

Correspondence to Yuan Yu.

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Li, X., Dong, L., Xiao, T. et al. TUFM: a central regulator in mitochondrial quality control and beyond. Cell Death Discov. (2026). https://doi.org/10.1038/s41420-026-03075-1

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  • Received: 18 November 2025

  • Revised: 27 February 2026

  • Accepted: 11 March 2026

  • Published: 28 March 2026

  • DOI: https://doi.org/10.1038/s41420-026-03075-1

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Cell Death Discovery (Cell Death Discov.)

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