Mitophagy is required for mitochondrial biogenesis and myogenic differentiation of C2C12 myoblasts
Open accessAbstract
Myogenesis is a crucial process governing skeletal muscle development and homeostasis. Differentiation of primitive myoblasts into mature myotubes requires a metabolic switch to support the increased energetic demand of contractile muscle. Skeletal myoblasts specifically shift from a highly glycolytic state to relying predominantly on oxidative phosphorylation (OXPHOS) upon differentiation. We have found that this phenomenon requires dramatic remodeling of the mitochondrial network involving both mitochondrial clearance and biogenesis. During early myogenic differentiation, autophagy is robustly upregulated and this coincides with DNM1L/DRP1 (dynamin 1-like)-mediated fragmentation and subsequent removal of mitochondria via SQSTM1 (sequestosome 1)-mediated mitophagy. Mitochondria are then repopulated via PPARGC1A/PGC-1α (peroxisome proliferator-activated receptor gamma, coactivator 1 alpha)-mediated biogenesis. Mitochondrial fusion protein OPA1 (optic atrophy 1 [autosomal dominant]) is then briskly upregulated, resulting in the reformation of mitochondrial networks. The final product is a myotube replete with new mitochondria. Respirometry reveals that the constituents of these newly established mitochondrial networks are better primed for OXPHOS and are more tightly coupled than those in myoblasts. Additionally, we have found that suppressing autophagy with various inhibitors during differentiation interferes with myogenic differentiation. Together these data highlight the integral role of autophagy and mitophagy in myogenic differentiation.
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Autophagy is critical for mitochondrial remodeling and function in skeletal muscle cells in vitro.
“autophagy is critical for mitochondrial remodeling and function in skeletal muscle cells in vitro (Sin et al., 2016)”
From Skeletal Muscle Ribosome and Mitochondrial Biogenesis in Response to Different Exercise Training Modalities (2021) · cites this paper as Sin et al., 2016
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- Authors
- Sin, J., Andres, A. M., Taylor, D. J. R., Weston, T., Hiraumi, Y., Stotland, A., Kim, B. J., Huang, C., Doran, K. S., & Gottlieb, R. A.
- Affiliations
- Cedars-Sinai Medical Center (US)
- San Diego State University (US)
- Corresponding author
- Gottlieb, Roberta A.
- ORCID
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2016-02-01
- Volume
- 12
- Issue
- 2
- Pages
- 369-380
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC4836019
- OpenAlex
- W2280853449
- Cited by
- 385
- References
- 24
- Citations by year
- 2026: 27 · 2025: 27 · 2024: 50 · 2023: 39 · 2022: 38 · 2021: 46 · 2020: 48 · 2019: 45 · 2018: 30 · 2017: 25 · 2016: 8 · 2015: 1
- FWCI
- 16.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Autophagy (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P01HL112730, T32HL116273)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- mitophagy, mitochondrial biogenesis, myogenesis, C2C12 myoblasts, Drp1, mitochondrial fragmentation, p62, PGC-1α, OPA1, mitochondrial fusion, oxidative phosphorylation, mitochondrial network remodeling, myotube formation, skeletal muscle development
- MeSH terms
- Animals, Organelle Biogenesis, Cell Differentiation, Cell Line, Mitochondria, Models, Biological, Oxidative Phosphorylation, Muscle Fibers, Skeletal, Macrolides, Muscle Development, Myoblasts, Mice, Mitophagy
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