Glutamine synthetase deficiency triggers mitochondrial oxidative stress and a ribotoxic stress response during acute hepatic metabolic crisis

Guihua Jin

doi:10.1016/j.metabol.2026.156730

Glutamine synthetase deficiency triggers mitochondrial oxidative stress and a ribotoxic stress response during acute hepatic metabolic crisis

2026-08-08

0

PRE

AI

G

Guihua Jin

C

Chengcheng Lin

Y

Yamei Wei

L

Lujia Zhu

D

Donghan Zhang

M

Miaotong Lin

Z

Zhenghui Wu

X

Xiaorong Chen

L

Longwang Chen

A

Aifang Sun *

Z

Zhongqiu Lu *

DOI：10.1016/j.metabol.2026.156730

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• GLUL deficiency triggers acute hepatic metabolic crisis and hepatotoxicity. • GLUL loss impairs TCA anaplerosis, fueling mitochondrial oxidative stress. • mtROS acts as a second messenger to activate ZAKα–JNK ribotoxic stress response. • MitoTEMPO or GLUL reconstitution rescues liver injury in vivo. • A novel GLUL–mtROS–RSR axis links glutamine metabolism to redox-driven cell death.

Glutamine synthetase deficiency triggers mitochondrial oxidative stress and a ribotoxic stress response during acute hepatic metabolic crisis

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