Nat Cell Biol | 一个酶连接两种命运：易聪/朱贵欣/孙启明团队发现肿瘤兼顾生长与存活的“代谢-自噬检查点”

TL;DR - A Nature Cell Biology paper (Zhejiang University; Yi Cong / Zhu Guixin / Sun Qiming, published 2026-07-29) reports that the glycolytic enzyme PGAM1 acts as a "metabolic–autophagy checkpoint," moonlighting as a scaffold that initiates autophagy independently of its catalytic activity. It matters because it reframes metabolic enzymes as direct cell-fate decision nodes and suggests tumors need both their metabolic "engine" and autophagic "resilience" blocked. Note: this is molecular cell biology, not AI research.

• In yeast, knockdown of the PGAM1 homolog Gpm1 blocked starvation-induced autophagy, while disabling only its glycolytic catalysis did not — separating the scaffolding function from enzymatic activity.
• Mechanistically, PGAM1/Gpm1 binds Atg9 (membrane supply) and Atg14 (PI3K complex I) to couple the two systems; the initiation kinase Atg1 (ULK1 in human cells) phosphorylates it under starvation to strengthen Atg14/ATG14 binding, a pathway conserved from yeast to mammals.
• PGAM1 is overexpressed in 30+ human malignancies; separation-of-function experiments show its glycolytic and autophagic roles independently drive tumor growth, and blocking either one suppresses progression while boosting the autophagy function accelerates tumorigenesis.
• Several clinically derived PGAM1 mutations leave glycolytic activity largely unchanged but increase autophagy-machinery binding and tumor growth, implying some metabolic-enzyme oncogenic mutations act via stress tolerance rather than faster metabolism — so catalytic-site-only inhibitors may be insufficient.