| Title: |
PFKM governs metabolic shifts throughout skeletal muscle differentiation |
| Authors: |
Campos, Melissa; Nguyen, Steven T; Kong, Xiangduo; Yang, Ying; Watson, Richard L; Gromova, Anastasia; Livelo, Catherine R; Franco, Carolina N; Cabral, Julia E; Seabrook, Laurence J; Dai, Shengqi; Liu, Yingzi; Zhou, Mingqi; Hanse, Eric A; Sumigray, Kaelyn; La Spada, Albert R; Seldin, Marcus M; Plikus, Maksim V; Nicholas, Dequina A; McNulty, Reginald; Kong, Mei; Yokomori, Kyoko; Albrecht, Lauren V |
| Source: |
Nature Metabolism, vol 8, iss 2 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2026 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
3205 Medical Biochemistry and Metabolomics (for-2020); 3208 Medical Physiology (for-2020); 32 Biomedical and Clinical Sciences (for-2020); 3210 Nutrition and Dietetics (for-2020); Stem Cell Research - Nonembryonic - Non-Human (rcdc); Stem Cell Research (rcdc); Nutrition (rcdc); 2.1 Biological and endogenous factors (hrcs-rac); Musculoskeletal (hrcs-hc); Cell Differentiation (mesh); Muscle; Skeletal (mesh); Animals (mesh); Mice (mesh); Glycolysis (mesh); Muscle Development (mesh); Humans (mesh); Phosphofructokinase-1 (mesh); Protein-Arginine N-Methyltransferases (mesh); Wnt Signaling Pathway (mesh) |
| Subject Geographic: |
489 - 505 |
| Description: |
Metabolism is known to influence cell identity, but the underlying mechanisms remain unclear. Here we reveal spatiotemporal dynamics of phosphofructokinase 1 (PFK1), a key glycolytic enzyme, within the skeletal muscle lineage. The expression of PFKM (the muscle isoform of PFK1) is low in muscle stem cells and increases during differentiation. Mechanistically, Wnt signalling rapidly induces lysosomal degradation of PFKM through a methyl arginine degron motif, which gets selectively methylated by the protein arginine methyltransferase (PRMT1) and delivered to lysosomes through microautophagy. PFKM degradation shifts glucose metabolism from glycolysis to the pentose phosphate pathway. PFKM overexpression increases glycolysis and promotes differentiation into terminally differentiated myofibres. On the other hand, PFKM knockdown blunts differentiation, which can be rescued by supplementation with the downstream glycolytic intermediate 3-phosphoglycerate. In sum, our findings highlight the importance of compartmentalized metabolism in cell fate decisions. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt84b6w504; https://escholarship.org/uc/item/84b6w504; https://escholarship.org/content/qt84b6w504/qt84b6w504.pdf |
| DOI: |
10.1038/s42255-026-01457-4 |
| Availability: |
https://escholarship.org/uc/item/84b6w504; https://escholarship.org/content/qt84b6w504/qt84b6w504.pdf; https://doi.org/10.1038/s42255-026-01457-4 |
| Rights: |
CC-BY |
| Accession Number: |
edsbas.69153105 |
| Database: |
BASE |