Wang, Liya
- Department of Animal Biosciences, Swedish University of Agricultural Sciences
Abstract
The importance of serine as a metabolic regulator is well known for tumors and is also gaining attention in degenerative diseases. Recent data indicate that de novo serine biosynthesis is an integral component of the metabolic response to mitochondrial disease, but the roles of the response have remained unknown. Here, we report that glucose-driven de novo serine biosynthesis maintains metabolic homeostasis in energetic stress. Pharmacological inhibition of the rate-limiting enzyme, phosphoglycerate dehydrogenase (PHGDH), aggravated mitochondrial muscle disease, suppressed oxidative phosphorylation and mitochondrial translation, altered whole-cell lipid profiles, and enhanced the mitochondrial integrated stress response (ISRmt) in vivo in skeletal muscle and in cultured cells. Our evidence indicates that de novo serine biosynthesis is essential to maintain mitochondrial respiration, redox balance, and cellular lipid homeostasis in skeletal muscle with mitochondrial dysfunction. Our evidence implies that interventions activating de novo serine synthesis may protect against mitochondrial failure in skeletal muscle.
Published in
Cell Reports
2025, volume: 44, number: 5, article number: 115710
Publisher: CELL PRESS
SLU Authors
UKÄ Subject classification
Cell Biology
Publication identifier
- DOI: https://doi.org/10.1016/j.celrep.2025.115710
Permanent link to this page (URI)
https://res.slu.se/id/publ/142203