Glutamine deficiency enhances nuclear localization of TCA cycle enzymes and epigenetic modifications, impairing myogenesis.

Angad Yadav, Susan Schmitt, Wenxia Ma, James A Mobley, Anna Elizabeth Thalacker-Mercer

Department of Cell Developmental and Integrative Biology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.Department of Cell Developmental and Integrative Biology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. · pubmed

Paper

Abstract

Extracellular glutamine (Gln) is essential for muscle progenitor cell (MPC) function and skeletal muscle regeneration / development, especially under physiological stress like aging or catabolic conditions. Gln availability regulates MPC proliferation by modulating intracellular metabolic and epigenetic states. Gln deficiency reduces cell viability, induces G0/G1 cell cycle arrest, and downregulates MyoD expression, collectively inhibiting myogenesis in human primary myoblasts (HSMM) and mouse C2C12 cells. Mechanistically, Gln deficiency enhances nuclear localization of TCA cycle enzyme, KGDHC, components (i.e., DLST and OGDH), elevates histone succinylation, and reduces chromatin accessibility at the myogenic regulatory regions (MyoD1 locus). These changes establish a direct link between Gln availability and an epigenetic-metabolic axis crucial for myogenic gene regulation. Thus, extracellular Gln acts as a key regulator of MPC proliferation through metabolic mediated control of chromatin state.

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Research summary

Glutamine deficiency impairs myogenesis by enhancing nuclear localization of TCA cycle enzymes and altering epigenetic modifications. This paper is relevant as it explores the metabolic and epigenetic mechanisms that influence muscle progenitor cell function, which is crucial for understanding muscle regeneration and potential interventions in age-related muscle decline.

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