Wang, Liya
- Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
Sammanfattning
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.
Publicerad i
Cell Reports
2025, volym: 44, nummer: 5, artikelnummer: 115710
Utgivare: CELL PRESS
SLU författare
UKÄ forskningsämne
Cellbiologi
Publikationens identifierare
- DOI: https://doi.org/10.1016/j.celrep.2025.115710
Permanent länk till denna sida (URI)
https://res.slu.se/id/publ/142203