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Updated: May 29, 2026

Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
A transport-independent role for SLC25A12 in mitochondrial stress signalling
Liu Jiang1, Lan Li1, Jialiang Guan1,2
1State Key Laboratory of Membrane Biology, New Cornerstone Science Laboratory, College of Future Technology, Peking University, Beijing, China.
Abstract:
Mitochondria are central hubs for energy production and cellular adaptation to stress. When mitochondria are damaged, cells activate protective signalling pathways to restore homeostasis and ensure survival. One such pathway, known as the integrated stress response (ISR), reduces overall protein synthesis while enhancing the production of stress-responsive proteins. The mitochondrial carriers SLC25A12 and SLC25A13 transport similar metabolites but are expressed in different tissues and linked to distinct genetic diseases. Here we show that SLC25A12 plays a previously unrecognized role in stress signalling that is independent of its transport activity. SLC25A12 interacts with the mitochondrial protease OMA1, enabling activation of ISR during mitochondrial damage. This signalling function is disrupted by a disease-linked mutation but preserved in transport-deficient variants. Our findings reveal SLC25A12 as a dual-function mitochondrial protein, acting as both a metabolite transporter and a regulator of stress signalling, and suggest that defective ISR activation may contribute to certain SLC25A12-associated pathologies.
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