Authors
Yi Zhang, Pengwei Zhao, Hangfei Liang, Zhaojie Liu, Shuling Dong, Yingcong Chen, Weijing Yao, Yuting Chen, Liting Yang, Zhonglan Shi, Lei Zhang, Yibin Pan, Fanghong Zheng, Qi Lin, Shichao Wang, Jinheng Pan, Mingzhu Fan, Shan Feng, Cheng Ma, Lifeng Pan, Ying Xing, Fan Yang, Shuiping Liu, Du Feng, Qiming Sun, Guixin Zhu, Cong Yi
Published in
Nature cell biology. Jul 29, 2026. Epub Jul 29, 2026.
Abstract
Cell survival requires tight coordination between growth-promoting metabolism and cellular quality-control pathways, yet how these processes are integrated remains unclear. Here we identify the conserved glycolytic enzyme PGAM1 as a metabolic-autophagy checkpoint that links glycolysis to autophagy initiation independently of its catalytic activity. Using complementary yeast and mammalian systems we show that PGAM1 functions as a molecular scaffold that recruits phosphatidylinositol 3-kinase complex I to the phagophore assembly site, thereby licensing autophagosome biogenesis. This autophagy-regulatory function is genetically essential, evolutionarily conserved and functionally separable from glycolysis. It is regulated by Atg1/ULK1-mediated phosphorylation that enhances Atg14 binding under starvation. Functionally, PGAM1 coordinates anabolic growth and stress-induced survival to maintain cellular homeostasis. In cancer, PGAM1 upregulation enhances both glycolytic flux and autophagy capacity. Disruption of either function markedly impairs tumour growth, establishing PGAM1 as a homeostatic checkpoint that is hijacked in cancer to drive both proliferation and stress tolerance.
PMID:
42527668
Bibliographic data and abstract were imported from PubMed on 30 Jul 2026.
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