De novo serine biosynthesis is protective in mitochondrial disease

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.23.533952v1?rss=1 Authors: Jackson, C. B., Marmyleva, A., Awadhpersad, R., Monteuuis, G., Mito, T., Zamboni, N., Tatsuta, T., Vincent, A. E., Wang, L., Langer, T., Carroll, C. J., Suomalainen-Wartiovaara, A. Abstract: Importance of serine as a metabolic regulator is well known in tumors and raising attention also in degenerative diseases. Recent data indicate that de novo serine biosynthesis is an integral component of 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 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 the skeletal muscle. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC