ArticleThe Journal of clinical investigation2022
A mitofusin 2/HIF1α axis sets a maturation checkpoint in regenerating skeletal muscle.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- Integrating and Orchestrating Multiple Components of Skeletal Muscle Injury and Regeneration.American journal of physiology. Cell physiology · 2026Article
- Hypoxia-inducible factor-1a (HIF1a) as a context-dependent integrator of metabolic stress in skeletal muscle.The Journal of physiology · 2026Review
- ANXA11 suppression restores muscular function in the mdx mouse model of Duchenne muscular dystrophy (DMD).Nature communications · 2026Article
- IRGM1-IRF7 Axis Controls Macrophage Chemotaxis to Orchestrate Skeletal Muscle Regeneration.Inflammation · 2026Article
- Senescent-Like Myofibers Contribute to Anti-Regenerative Cytokine Signaling in Duchenne Muscular Dystrophy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Understanding the role of NOTCH2 mutation in centronuclear myopathy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Perspectives on mitochondrial dysfunction in the regeneration of aging skeletal muscle.Cellular & molecular biology letters · 2025Review
- Metabolic inflexibility promotes mitochondrial health during liver regeneration.Science (New York, N.Y.) · 2024Article
- Developmental dynamics of mitochondrial fission and fusion proteins in functionally divergent skeletal muscles of goat.Physiological reports · 2024Article
- The long-term health outcomes, pathophysiological mechanisms and multidisciplinary management of long COVID.Signal transduction and targeted therapy · 2023Review
- Regenerating Myofibers after an Acute Muscle Injury: What Do We Really Know about Them?International journal of molecular sciences · 2023Review
- The Role of Mitochondria in Mediation of Skeletal Muscle Repair.Muscles (Basel, Switzerland) · 2023Review
- Neuromuscular disease: 2023 update.Free neuropathology · 2023Article
- Not young but still immature: a HIF-1α-mediated maturation checkpoint in regenerating muscle.The Journal of clinical investigation · 2022Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
A fundamental issue in regenerative medicine is whether there exist endogenous regulatory mechanisms that limit the speed and efficiency of the repair process. We report the existence of a maturation checkpoint during muscle regeneration that pauses myofibers at a neonatal stage. This checkpoint is regulated by the mitochondrial protein mitofusin 2 (Mfn2), the expression of which is activated in response to muscle injury. Mfn2 is required for growth and maturation of regenerating myofibers; in the absence of Mfn2, new myofibers arrested at a neonatal stage, characterized by centrally nucleated myofibers and loss of H3K27me3 repressive marks at the neonatal myosin heavy chain gene. A similar arrest at the neonatal stage was observed in infantile cases of human centronuclear myopathy. Mechanistically, Mfn2 upregulation suppressed expression of hypoxia-induced factor 1α (HIF1α), which is induced in the setting of muscle damage. Sustained HIF1α signaling blocked maturation of new myofibers at the neonatal-to-adult fate transition, revealing the existence of a checkpoint that delays muscle regeneration. Correspondingly, inhibition of HIF1α allowed myofibers to bypass the checkpoint, thereby accelerating the repair process. We conclude that skeletal muscle contains a regenerative checkpoint that regulates the speed of myofiber maturation in response to Mfn2 and HIF1α activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.