Loss of ULK1 and ULK2 drives muscle growth in mice but impairs force
While lifelong depletion reduced muscle strength, short-term deficiency in adult mice induced hypertrophy without degrading muscle quality or contractile performance.
bioRxiv : the preprint server for biology · Son W et al. · Paper published 10 Sep 2026
In a preprint study using mice, researchers examined how the autophagy-initiating kinases ULK1 and ULK2 control muscle mass and protein metabolism. The team evaluated mice with skeletal muscle-specific knockouts of Ulk1 and Ulk2 alongside adult mice given short-term microRNA knockdowns. Lifelong loss of both kinases blocked autophagy flux, increased centrally nucleated fibers, and reduced muscle force by 20 to 24 percent. However, it also induced muscle hypertrophy, boosting fiber diameters by 10 to 20 percent. Mechanistically, ULK1 and ULK2 deficiency elevated myofibrillar protein synthesis by 23 percent, decreased sarcoplasmic protein degradation, and activated mTORC1 independently of AKT. In contrast, short-term depletion of the kinases in adult mice produced a 13 percent increase in myofiber size without causing force deficits or structural markers of muscle damage.
Why it matters
Maintaining muscle mass and function relies on a fine balance between protein synthesis and degradation. Identifying ULK1 and ULK2 as regulators of both pathways highlights a potential node to explore for treating muscle atrophy.
Caveats
The findings come from mouse models and have not yet undergone peer review because the report is a preprint. Whether transient inhibition of ULK1 and ULK2 can safely prevent muscle wasting in humans remains unknown.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
ULK1 and ULK2 Restrain Skeletal Myofiber Growth by Balancing Protein Synthesis and Degradation
Son W, Fuqua J, Harris MP et al.
bioRxiv : the preprint server for biology · 10 Sep 2026 · Preprint, not yet peer-reviewed
- Relevance
- Relevant
- News value
- Notable
- Evidence
- Animals
- Status
- Preprint
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