Spermidine-eIF5A Axis is Essential for Muscle Stem Cell Activation Via Translational Control

Overview

Journal Cell Discov

Date 2024 Sep 9

PMID 39251577

Authors

Qianying Zhang

Wanhong Han

Rimao Wu

Shixian Deng

Jiemiao Meng

Yuanping Yang

Lili Li

Mingwei Sun

Heng Ai

Yingxi Chen

Qinyao Liu

Tian Gao

Xingchen Niu

Haixia Liu

Li Zhang

Dan Zhang

Meihong Chen

Pengbin Yin

Licheng Zhang

Peifu Tang

Dahai Zhu

Yong Zhang

Hu Li

Affiliations

Soon will be listed here.

Abstract

Adult skeletal muscle stem cells, also known satellite cells (SCs), are quiescent and activate in response to injury. However, the activation mechanisms of quiescent SCs (QSCs) remain largely unknown. Here, we investigated the metabolic regulation of SC activation by identifying regulatory metabolites that promote SC activation. Using targeted metabolomics, we found that spermidine acts as a regulatory metabolite to promote SC activation and muscle regeneration in mice. Mechanistically, spermidine activates SCs via generating hypusinated eIF5A. Using SC-specific eIF5A-knockout (KO) and Myod-KO mice, we further found that eIF5A is required for spermidine-mediated SC activation by controlling MyoD translation. More significantly, depletion of eIF5A in SCs results in impaired muscle regeneration in mice. Together, the findings of our study define a novel mechanism that is essential for SC activation and acts via spermidine-eIF5A-mediated MyoD translation. Our findings suggest that the spermidine-eIF5A axis represents a promising pharmacological target in efforts to activate endogenous SCs for the treatment of muscular disease.

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