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Mitochondrial Dynamics Is a Distinguishing Feature of Skeletal Muscle Fiber Types and Regulates Organellar Compartmentalization
Open accessAbstract
Skeletal muscle fibers differentiate into specific fiber types with distinct metabolic properties determined by their reliance on oxidative phosphorylation (OXPHOS). Using in vivo approaches, we find that OXPHOS-dependent fibers, compared to glycolytic fibers, contain elongated mitochondrial networks with higher fusion rates that are dependent on the mitofusins Mfn1 and Mfn2. Switching of a glycolytic fiber to an oxidative IIA type is associated with elongation of mitochondria, suggesting that mitochondrial fusion is linked to metabolic state. Furthermore, we reveal that mitochondrial proteins are compartmentalized to discrete domains centered around their nuclei of origin. The domain dimensions are dependent on fiber type and are regulated by the mitochondrial dynamics proteins Mfn1, Mfn2, and Mff. Our results indicate that mitochondrial dynamics is tailored to fiber type physiology and provides a rationale for the segmental defects characteristic of aged and diseased muscle fibers.
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“type I muscle fibres have been shown to display a different mitochondrial topology compared with type II fibres, with mitochondria appearing more elongated and ‘string-like’ [43].”
From Human skeletal muscle mitochondrial dynamics in relation to oxidative capacity and insulin sensitivity (2021) · cites this paper as [43]
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“Therefore, the mitochondrial network morphology, arrangement, and connectivity adapt to each fiber type's specific functional needs (e.g., OXPHOS capacity and contractility) [31, 32].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [31]
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“Other studies have also highlighted that mitochondrial morphology and dynamics differ across muscle fiber types [61,66,67].”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [66]
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Metadata
- Authors
- Mishra, P., Varuzhanyan, G., Pham, A. H., & Chan, D. C.
- Affiliations
- California Institute of Technology (US)
- Corresponding author
- Chan, David C.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 22
- Issue
- 6
- Pages
- 1033-1044
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4670593
- OpenAlex
- W1940751968
- Cited by
- 290
- References
- 49
- Citations by year
- 2026: 18 · 2025: 22 · 2024: 45 · 2023: 44 · 2022: 28 · 2021: 29 · 2020: 36 · 2019: 20 · 2018: 22 · 2017: 11 · 2016: 15
- FWCI
- 6.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM062967, R25GM076162, GM062967, T32 GM0076162, R01GM110039)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- mitochondrial dynamics, skeletal muscle fiber types, mitochondrial fusion, mitofusins, Mfn1, mitofusin 2, mitochondrial fission, Mff, oxidative phosphorylation, glycolytic fibers, mitochondrial compartmentalization, muscle aging, myopathy
- MeSH terms
- Animals, Luminescent Proteins, Membrane Proteins, Mice, Transgenic, Microscopy, Electron, Mitochondria, Oxidative Phosphorylation, Muscle Fibers, Skeletal, GTP Phosphohydrolases, Mitochondrial Proteins, Mice, Gene Knock-In Techniques, Time-Lapse Imaging, Mitochondrial Dynamics
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