2. Academic Validation
  3. TNF-α-Induced KAT2A Impedes BMMSC Quiescence by Mediating Succinylation of the Mitophagy-Related Protein VCP

TNF-α-Induced KAT2A Impedes BMMSC Quiescence by Mediating Succinylation of the Mitophagy-Related Protein VCP

  • Adv Sci (Weinh). 2023 Dec 25:e2303388. doi: 10.1002/advs.202303388.
Zepeng Su 1,  Jinteng Li 1,  Jiajie Lin 1,  Zhikun Li 1,  Yunshu Che 1,  Zhaoqiang Zhang 1,  Guan Zheng 1,  Guiwen Ye 1,  Wenhui Yu 1,  Yipeng Zeng 1,  Peitao Xu 1,  Xiaojun Xu 1,  Zhongyu Xie 1,  Yanfeng Wu 2,  Huiyong Shen 1
Affiliations

Affiliations

  • 1 Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518000, China.
  • 2 Center for Biotherapy, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518000, China.
PMID: 38145956 DOI: 10.1002/advs.202303388
Abstract

Regular quiescence and activation are important for the function of bone marrow mesenchymal stem cells (BMMSC), multipotent stem cells that are widely used in the clinic due to their capabilities in tissue repair and inflammatory disease treatment. TNF-α is previously reported to regulate BMMSC functions, including multilineage differentiation and immunoregulation. The present study demonstrates that TNF-α impedes quiescence and promotes the activation of BMMSC in vitro and in vivo. Mechanistically, the TNF-α-induced expression of KAT2A promotes the succinylation of VCP at K658, which inhibits the interaction between VCP and MFN1 and thus inhibits Mitophagy. Furthermore, activated BMMSC exhibits stronger fracture repair and immunoregulation functions in vivo. This study contributes to a better understanding of the mechanisms of BMMSC quiescence and activation and to improving the effectiveness of BMMSC in clinical applications.

Keywords

BMMSC; TNF-α; mitophagy; quiescence; succinylation.

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