2. Academic Validation
  3. Deacetylation of GLUD1 maintains the survival of lung adenocarcinoma cells under glucose starvation by inhibiting autophagic cell death

Deacetylation of GLUD1 maintains the survival of lung adenocarcinoma cells under glucose starvation by inhibiting autophagic cell death

  • Cell Insight. 2024 Jul 16;3(5):100186. doi: 10.1016/j.cellin.2024.100186.
Qifan Hu 1 2 3,  Longhua Sun 1,  Zhujun Cheng 4,  Lei Wang 5,  Xiaorui Wan 1,  Jing Xu 5,  Junyao Cheng 1,  Zuorui Wang 5,  Yi Yuan 6,  Keru Wang 6,  Tianyu Han 1 7
Affiliations

Affiliations

  • 1 Jiangxi Provincial Key Laboratory of Respirtory Diseases, Jiangxi Institute of Respiratory Diseases, The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
  • 2 Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.
  • 3 Postdoctoral Innovation Practice Base, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
  • 4 Department of Burn, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.
  • 5 School of Basic Medical Sciences, Nanchang University, Nanchang, 330031, Jiangxi, China.
  • 6 School of Huankui Academy, Nanchang University, Nanchang, 330031, Jiangxi, China.
  • 7 China-Japan Friendship Jiangxi Hospital, National Regional Center for Respiratory Medicine, Nanchang, 330200, Jiangxi, China.
PMID: 39144257 DOI: 10.1016/j.cellin.2024.100186
Abstract

Enhanced glutamine catabolism is one of the main metabolic features of Cancer, providing energy and intermediate metabolites for Cancer progression. However, the functions of glutamine catabolism in Cancer under nutrient deprivation need to be further clarified. Here, we discovered that deacetylation of glutamate dehydrogenase 1 (GLUD1), one of the key Enzymes in glutamine catabolism, maintains the survival of lung adenocarcinoma (LUAD) cells under glucose starvation by inhibiting autophagic cell death. We found that glucose starvation increased GLUD1 activity by reducing its acetylation on Lys84 and promoted its active hexamer formation. Besides, deacetylation of GLUD1 induced its cytoplasmic localization, where GLUD1 was ubiquitinated in K63-linkage by TRIM21, leading to the binding of GLUD1 with cytoplasmic Glutaminase KGA. These two effects enhanced glutamine metabolism both in mitochondria and cytoplasm, increased the production of alpha-ketoglutarate (α-KG). Meanwhile, cytoplasmic GLUD1 also interacted with p62 and prevented its acetylation, leading to the inhibition of p62 body formation. All these effects blocked autophagic cell death of LUAD cells under glucose starvation. Taken together, our results reveal a novel function of GLUD1 under glucose deprivation in LUAD cells and provide new insights into the functions of glutamine catabolism during Cancer progression.

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