Serine synthesis pathway enzyme PHGDH is critical for muscle cell biomass, anabolic metabolism, and mTORC1 signaling
Open accessAbstract
The use of glycolytic intermediates for anabolism was demonstrated in both myoblasts and myotubes, which incorporate glucose-derived carbon into proteins, RNA, and lipids. We identify phosphoglycerate dehydrogenase (PHGDH) as a critical enzyme in those processes and also for muscle cell hypertrophy, proliferation, protein synthesis, and mTORC1 signaling. Our results thus suggest that PHGDH in skeletal muscle is more than just a serine-synthesizing enzyme.
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The serine biosynthesis pathway is crucial for skeletal muscles to generate cell biomass, because inhibition of serine biosynthesis, but not other pathways, decreased protein synthesis, myotube size, and myoblast proliferation in an mTORC1-dependent manner.
“It was the serine biosynthesis pathway that was crucial for skeletal muscles to generate cell biomass, because the inhibition of serine biosynthesis, but not of the other pathways, decreased protein synthesis, myotube size, and the proliferation of myoblast cells in an mTORC1-dependent manner [53].”
From 20-Hydroxyecdysone Boosts Energy Production and Biosynthetic Processes in Non-Transformed Mouse Cells (2024) · cites this paper as [53]
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- Authors
- Mäntyselkä, S., Kolari, K., Baumert, P., Ylä-Outinen, L., Kuikka, L., Lahtonen, S., Permi, P., Wackerhage, H., Kalenius, E., Kivelä, R., & Hulmi, J. J.
- Affiliations
- University of Jyväskylä (FI)
- Technical University of Munich (DE)
- Faculty of Sport and Health Sciences, NeuroMuscular Research Center, University of Jyväskylä, Jyväskylä, Finland
- Central Finland Health Care District (FI)
- University of Helsinki (FI)
- Corresponding author
- Kolari, Kalle
- Baumert, Philipp
- Wackerhage, Henning
- Kalenius, Elina
- Kivelä, Riikka
- ORCID
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2024-01-01
- Volume
- 326
- Issue
- 1
- Pages
- E73-E91
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W4388900575
- Cited by
- 25
- References
- 58
- Citations by year
- 2026: 11 · 2025: 9 · 2024: 5
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- green
- urn.fi
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Jyväskylä University Digital Archive (University of Jyväskylä) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Työväentutkimus Vuosikirja (submittedVersion, other-oa)
- Funders
- Academy of Finland (301824)
- EC | HORIZON EUROPE Framework Programme (754462)
- Emil Aaltosen Säätiö
- Jyväskylän Yliopisto
- Suomen Kulttuurirahasto
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- PHGDH, serine biosynthesis, skeletal muscle, muscle cell proliferation, protein synthesis, mTORC1 signaling, glycolytic intermediates, anabolic metabolism, myoblasts, myotubes
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Animals, Carbon, Glucose, Humans, Lipids, RNA, Serine, Muscle Fibers, Skeletal, Biomass, Cell Proliferation, Phosphoglycerate Dehydrogenase, Mice
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