Mitochondrial reticulum for cellular energy distribution in muscle
Open accessAbstract
Intracellular energy distribution has attracted much interest and has been proposed to occur in skeletal muscle via metabolite-facilitated diffusion; however, genetic evidence suggests that facilitated diffusion is not critical for normal function. We hypothesized that mitochondrial structure minimizes metabolite diffusion distances in skeletal muscle. Here we demonstrate a mitochondrial reticulum providing a conductive pathway for energy distribution, in the form of the proton-motive force, throughout the mouse skeletal muscle cell. Within this reticulum, we find proteins associated with mitochondrial proton-motive force production preferentially in the cell periphery and proteins that use the proton-motive force for ATP production in the cell interior near contractile and transport ATPases. Furthermore, we show a rapid, coordinated depolarization of the membrane potential component of the proton-motive force throughout the cell in response to spatially controlled uncoupling of the cell interior. We propose that membrane potential conduction via the mitochondrial reticulum is the dominant pathway for skeletal muscle energy distribution.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Recent high-resolution 3D microscopy findings challenged the existence of two separated mitochondrial pools and strengthened the concept of a physically and functionally highly interconnected mitochondrial network in skeletal muscle.
“Recent findings on high-resolution three-dimensional microscopy challenged the existence of two separated mitochondrial pools and strengthened the concept of a physically and functionally highly interconnected mitochondrial network in skeletal muscle [21, 24, 26].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [24]
The mitochondrial muscle reticulum forms a conductive pathway that can rapidly transfer energy from the capillary to the contractile apparatus.
“The mitochondrial muscle reticulum forms a conductive pathway that can rapidly transfer energy from the oxygen source, the capillary, to the contractile apparatus [24].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [24]
Mitochondrial fusion enables redistribution of energy in the form of mitochondrial potential, metabolites, proteins, and mtDNA, improving calcium handling and ATP synthesis.
“This process enables the redistribution of energy in the form of mitochondrial potential, metabolites, proteins, and mtDNA, improving calcium handling, and ATP synthesis [24, 54–57].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [24]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Computer visualization of three-dimensional image data using IMOD.
Kremer, J. R., Mastronarde, D., & Mcintosh, J. (1996) · Journal of Structural Biology · doi:10.1006/jsbi.1996.0013 · Cited by 5,770 · see citing works
Serial Block-Face Scanning Electron Microscopy to Reconstruct Three-Dimensional Tissue Nanostructure
Denk, W., & Horstmann, H. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020329 · Cited by 1,644 · see citing works
Transport of Energy in Muscle: The Phosphorylcreatine Shuttle
Bessman, S. P., & Geiger, P. J. (1981) · Science · doi:10.1126/science.6450446 · Cited by 761 · see citing works
Myoglobin-facilitated oxygen diffusion: role of myoglobin in oxygen entry into muscle.
Wittenberg, J. B. (1970) · Physiological Reviews · doi:10.1152/physrev.1970.50.4.559 · Cited by 573 · see citing works
Wittig, I., Karas, M., & Schägger, H. (2007) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m700076-mcp200 · Cited by 552 · see citing works
Skeletal muscles of mice deficient in muscle creatine kinase lack burst activity
van Deursen, J., Heerschap, A., Oerlemans, F. T. J. J., Rultenbeek, W., Jap, P. H. K., Laak, H. T., & Wieringa, B. (1993) · Cell · doi:10.1016/0092-8674(93)90510-w · Cited by 343 · see citing works
Exercise-induced maximal metabolic rate scales with muscle aerobic capacity
Weibel, E. R., & Hoppeler, H. H. (2005) · Journal of Experimental Biology · doi:10.1242/jeb.01548 · Cited by 325 · see citing works
Garry, D. J., Ordway, G. A., Lorenz, J. N., Radford, N. B., Chin, E. R., Grange, R. W., Bassel‐Duby, R., & Williams, R. S. (1998) · Nature · doi:10.1038/27681 · Cited by 289 · see citing works
Amchenkova, A. A., Bakeeva, L. E., Chentsov, Y. S., Skulachev, V. P., & Zorov, D. B. (1988) · The Journal of cell biology · doi:10.1083/jcb.107.2.481 · Cited by 284 · see citing works
Mitochondrial framework (reticulum mitochondriale) in rat diaphragm muscle
Bakeeva, L. E., Chentsov, Y. S., & Skulachev, V. P. (1978) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(78)90104-4 · Cited by 227 · see citing works
Energy Transformations in the Respiratory Chain
Skulachev, V. P. (1971) · Current topics in bioenergetics · doi:10.1016/b978-0-12-152504-0.50010-1 · Cited by 222 · see citing works
Mitochondrial reticulum in limb skeletal muscle
Kirkwood, S. P., Munn, E. A., & Brooks, G. A. (1986) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1986.251.3.c395 · Cited by 179 · see citing works
Mitochondrial fusion is frequent in skeletal muscle and supports excitation–contraction coupling
Eisner, V., Lenaers, G., & Hajnóczky, G. (2014) · Journal of Cell Biology · doi:10.1083/jcb.201312066 · Cited by 177 · see citing works
H2O2-induced mitochondrial fragmentation in C2C12 myocytes
Fan, X., Hussien, R., & Brooks, G. A. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.08.024 · Cited by 172 · see citing works
Acute exercise remodels mitochondrial membrane interactions in mouse skeletal muscle
Picard, M. A., Gentil, B. J., McManus, M. J., White, K., Louis, K. S., Gartside, S. E., Wallace, D. C., & Turnbull, D. M. (2013) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00819.2013 · Cited by 145 · see citing works
Stimulated Emission Depletion Nanoscopy of Living Cells Using SNAP-Tag Fusion Proteins
Hein, B., Willig, K. I., Wurm, C. A., et al. (2010) · Biophysical Journal · doi:10.1016/j.bpj.2009.09.053 · Cited by 129 · see citing works
Chalmers, S., Caldwell, S. T., Quin, C., Prime, T. A., James, A. M., Cairns, A. G., Murphy, M. P., McCarron, J. G., & Hartley, R. C. (2011) · Journal of the American Chemical Society · doi:10.1021/ja2077922 · Cited by 118 · see citing works
Dahl, R., Larsen, S., Dohlmann, T. L., Qvortrup, K., Helge, J. W., Dela, F., & Prats, C. (2015) · Acta Physiologica · doi:10.1111/apha.12289 · Cited by 111 · see citing works
Narayan, K., Danielson, C. M., Lagarec, K., Lowekamp, B., Coffman, P., Laquerre, A., Phaneuf, M. W., Hope, T. J., & Subramaniam, S. (2013) · Journal of Structural Biology · doi:10.1016/j.jsb.2013.11.008 · Cited by 105 · see citing works
Self-citationLygate, C. A., Aksentijević, D., Dawson, D. K., ten Hove, M., Phillips, D. J., de Bono, J. P., Medway, D. J., Sebag‐Montefiore, L., Hunyor, I., Channon, K. M., et al. (2013) · Circulation Research · doi:10.1161/circresaha.112.300725 · Cited by 104 · see citing works
Self-citationOgata, T., & Yamasaki, Y. (1985) · Cell and Tissue Research · doi:10.1007/bf00217168 · Cited by 98 · see citing works
Balaban, R. S., Mootha, V. K., & Arai, A. E. (1996) · Analytical Biochemistry · doi:10.1006/abio.1996.0239 · Cited by 86 · see citing works
Self-citationProtein composition and function of red and white skeletal muscle mitochondria
Glancy, B. C., & Balaban, R. S. (2011) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00496.2010 · Cited by 86 · see citing works
Self-citationCorrelative 3D imaging of whole mammalian cells with light and electron microscopy
Murphy, G. E., Narayan, K., Lowekamp, B., Hartnell, L. M., Heymann, J. A. W., Fu, J. W., & Subramaniam, S. (2011) · Journal of Structural Biology · doi:10.1016/j.jsb.2011.08.013 · Cited by 85 · see citing works
Self-citationRothstein, E. C., Carroll, S. L., Combs, C. A., et al. (2005) · Biophysical Journal · doi:10.1529/biophysj.104.053165 · Cited by 79 · see citing works
Self-citationEffects of endurance training on a mitochondrial reticulum in limb skeletal muscle
Kirkwood, S. P., Packer, L., & Brooks, G. A. (1987) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(87)90296-7 · Cited by 77 · see citing works
Mitochondrial size and shape in equine skeletal muscle: A three‐dimensional reconstruction study
Kayar, S. R., Hoppeler, H. H., Mermod, L., & Weibel, E. R. (1988) · The Anatomical Record · doi:10.1002/ar.1092220405 · Cited by 73 · see citing works
Changes in the mitochondrial proteome from mouse hearts deficient in creatine kinase
Kernec, F., Ünlü, M., Labeikovsky, W., Minden, J. S., & Koretsky, A. P. (2001) · Physiological Genomics · doi:10.1152/physiolgenomics.2001.6.2.117 · Cited by 58 · see citing works
Glancy, B. C., Hsu, L., Dao, L. H., Bakalar, M. H., French, S. A., Chess, D. J., Taylor, J. F., Picard, M. A., Aponte, A. M., Daniels, M. P., et al. (2014) · Microcirculation · doi:10.1111/micc.12098 · Cited by 56 · see citing works
Self-citationOntogenesis of mitochondrial reticulum in rat diaphragm muscle.
Bakeeva, L. E., Chentsov, Y. S., & Skulachev, V. P. (1981) · PubMed · Cited by 56 · see citing works
Die d�nnen und die dicken Muskelfasern des Zwerchfells der Ratte
Bubenzer, H. J. (1966) · Cell and Tissue Research · doi:10.1007/bf00406300 · Cited by 49 · see citing works
MEMBRANE JUNCTIONS IN THE INTERMEMBRANE SPACE OF MITOCHONDRIA FROM MAMMALIAN TISSUES
Saito, A., Smigel, M. D., & Fleischer, S. (1974) · The Journal of Cell Biology · doi:10.1083/jcb.60.3.653 · Cited by 31 · see citing works
Three‐dimensional motion tracking for high‐resolution optical microscopy, in vivo
Bakalar, M. H., Schroeder, J., Pursley, R. H., Pohida, T. J., Glancy, B. C., TAYLOR, J., Chess, D. J., Kellman, P., XUE, H., & Balaban, R. S. (2012) · Journal of Microscopy · doi:10.1111/j.1365-2818.2012.03613.x · Cited by 20 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 2
- [28]Bakalar M Three-dimensional motion tracking for high-resolution optical microscopy, in vivo. J. Microsc 246, 237– 247 (2012). 22582797 PMC3799900
- [29]Narayan K Multi-resolution correlative focused ion beam scanning electron microscopy: applications to cell biology. J. Struct. Biol 185, 278– 284 (2014). 24300554 PMC3943650
Cited by
Sorted by citations
Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease
Smith, R. L., Soeters, M. R., Wüst, R. C. I., & Houtkooper, R. H. (2018) · Endocrine Reviews · doi:10.1210/er.2017-00211 · Cited by 787 · see citing works
Mitochondrial quality control and muscle mass maintenance.
Romanello, V., & Sandri, M. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2015.00422 · Cited by 434 · see citing works
Exercise Metabolism and Adaptation in Skeletal Muscle
Smith, J. A. B., Murach, K. A., Dyar, K. A., & Zierath, J. R. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00606-x · Cited by 342 · see citing works
Egan, B., & Sharples, A. P. (2023) · Physiological Reviews · doi:10.1152/physrev.00054.2021 · Cited by 278 · see citing works
Skeletal muscle mitochondria as a target to prevent or treat type 2 diabetes mellitus
Hesselink, M. K. C., Schrauwen-Hinderling, V., & Schrauwen, P. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.104 · Cited by 242 · see citing works
Role of Age-Related Mitochondrial Dysfunction in Sarcopenia
Ferri, E., Marzetti, E., Calvani, R., Picca, A., Cesari, M., & Arosio, B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21155236 · Cited by 224 · see citing works
Roberts, M. D., McCarthy, J. J., Hornberger, T. A., Phillips, S. M., Mackey, A. L., Nader, G. A., Boppart, M. D., Kavazis, A. N., Reidy, P. T., Ogasawara, R., et al. (2023) · Physiological Reviews · doi:10.1152/physrev.00039.2022 · Cited by 214 · see citing works
Romanello, V., & Sandri, M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03662-0 · Cited by 197 · see citing works
Quantitative 3D Mapping of the Human Skeletal Muscle Mitochondrial Network
Vincent, A. E., White, K., Davey, T., Philips, J., Ogden, R. T., Lawless, C., Warren, C., Hall, M. G., Ng, Y. S., Falkous, G., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.01.010 · Cited by 195 · see citing works
Power Grid Protection of the Muscle Mitochondrial Reticulum
Glancy, B., Hartnell, L. M., Combs, C. A., Femnou, A., Sun, J., Murphy, E., Subramaniam, S., & Balaban, R. S. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.03.063 · Cited by 172 · see citing works
Self-citationBishop, D. J., Botella, J., Genders, A. J., Lee, M. J.-C., Saner, N. J., Kuang, J., Yan, X., & Granata, C. (2019) · Physiology · doi:10.1152/physiol.00038.2018 · Cited by 180 · see citing works
Subcellular connectomic analyses of energy networks in striated muscle
Bleck, C. K. E., Kim, Y., Willingham, T. B., & Glancy, B. (2018) · Nature Communications · doi:10.1038/s41467-018-07676-y · Cited by 150 · see citing works
Self-citationLactate as a myokine and exerkine: drivers and signals of physiology and metabolism
Brooks, G. A., Osmond, A. D., Arevalo, J. A., Duong, J. J., Curl, C. C., Moreno-Santillan, D. D., & Leija, R. G. (2023) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00497.2022 · Cited by 171 · see citing works
Unravelling the mechanisms regulating muscle mitochondrial biogenesis
Hood, D. A., Tryon, L. D., Carter, H. N., Kim, Y., & Chen, C. C. W. (2016) · Biochemical Journal · doi:10.1042/bcj20160009 · Cited by 159 · see citing works
Exercise Induces Tissue-Specific Adaptations to Enhance Cardiometabolic Health
Ashcroft, S. P., Stocks, B., Egan, B., & Zierath, J. R. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2023.12.008 · Cited by 149 · see citing works
Exercise and mitochondrial dynamics: keeping in shape with ROS and AMPK
Trewin, A., Berry, B., & Wojtovich, A. (2018) · Antioxidants · doi:10.3390/antiox7010007 · Cited by 129 · see citing works
The Interplay between Mitochondrial Morphology and Myomitokines in Aging Sarcopenia
Romanello, V. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010091 · Cited by 101 · see citing works
Avellaneda, J., Rodier, C., Daian, F., Brouilly, N., Rival, T., Luis, N. M., & Schnorrer, F. (2021) · Nature Communications · doi:10.1038/s41467-021-22058-7 · Cited by 92 · see citing works
Wyckelsma, V. L., Levinger, I., McKenna, M. J., Formosa, L. E., Ryan, M. T., Petersen, A. C., Anderson, M. J., & Murphy, R. M. (2017) · The Journal of Physiology · doi:10.1113/jp273950 · Cited by 91 · see citing works
Halling, J. F., Ringholm, S., Olesen, J., Prats, C., & Pilegaard, H. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.05.020 · Cited by 86 · see citing works
Exercise is muscle mitochondrial medicine
Oliveira, A. N., Richards, B. J., Slavin, M., & Hood, D. A. (2021) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000250 · Cited by 26 · see citing works
- Authors
- Glancy, B., Hartnell, L. M., Malide, D., Yu, Z.-X., Combs, C. A., Connelly, P. S., Subramaniam, S., & Balaban, R. S.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Balaban, Robert S.
- ORCID
- Venue
- Nature
- Published
- 2015-07
- Volume
- 523
- Issue
- 7562
- Pages
- 617-620
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6988728
- OpenAlex
- W1766184155
- Cited by
- 450
- References
- 33
- Citations by year
- 2026: 22 · 2025: 37 · 2024: 50 · 2023: 51 · 2022: 43 · 2021: 51 · 2020: 49 · 2019: 37 · 2018: 50 · 2017: 25 · 2016: 28 · 2015: 7
- FWCI
- 15.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (Z01HL004601)
- National Cancer Institute (ZIABC010278, Z01BC010278)
- NHLBI Division of Intramural Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- mitochondrial reticulum, mitochondrial membrane potential, proton motive force, skeletal muscle, mitochondrial protein localization, uncoupling, ATP production
- MeSH terms
- Adenosine Triphosphatases, Adenosine Triphosphate, Animals, Diffusion, Energy Metabolism, Male, Mice, Inbred C57BL, Mitochondria, Muscle, Muscle, Skeletal, Proton-Motive Force, Mitochondrial Proteins, Mice, Membrane Potential, Mitochondrial
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
