The DOI matches its Crossref record; 82 of the 82 references it cites were found in a registry or an index.
pH-Gated Succinate Secretion Regulates Muscle Remodeling in Response to Exercise
Open accessAbstract
In response to skeletal muscle contraction during exercise, paracrine factors coordinate tissue remodeling, which underlies this healthy adaptation. Here we describe a pH-sensing metabolite signal that initiates muscle remodeling upon exercise. In mice and humans, exercising skeletal muscle releases the mitochondrial metabolite succinate into the local interstitium and circulation. Selective secretion of succinate is facilitated by its transient protonation, which occurs upon muscle cell acidification. In the protonated monocarboxylic form, succinate is rendered a transport substrate for monocarboxylate transporter 1, which facilitates pH-gated release. Upon secretion, succinate signals via its cognate receptor SUCNR1 in non-myofibrillar cells in muscle tissue to control muscle-remodeling transcriptional programs. This succinate-SUCNR1 signaling is required for paracrine regulation of muscle innervation, muscle matrix remodeling, and muscle strength in response to exercise training. In sum, we define a bioenergetic sensor in muscle that utilizes intracellular pH and succinate to coordinate tissue adaptation to exercise.
Overview
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
Verification
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?
In the citing paper
“This release occurs in a pH-dependent manner via monocarboxylate transporter 1 and is facilitated by transient protonation of succinate upon muscle cell acidification (191).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [191]
In the citing paper
“Circulating succinate binds its receptor SUCNR1 in nonmyofibrillar cells in muscle tissue to initiate transcriptional programs that support tissue remodeling in response to exercise (191).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [191]
In the citing paper
“Notably, both mouse and human muscle cells selectively release succinate during physical activity (191).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [191]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Trapnell, C., Roberts, A., Goff, L. A., Pertea, G. M., Kim, D., Kelley, D. R., Pimentel, H., Salzberg, S. L., Rinn, J. L., & Pachter, L. S. (2012) · Nature Protocols · doi:10.1038/nprot.2012.016 · Cited by 12,145
Enrichr: a comprehensive gene set enrichment analysis web server 2016 update
Kuleshov, M. V., Jones, M. R., Rouillard, A. D., Fernandez, N. F., Duan, Q., Wang, Z., Koplev, S., Jenkins, S. L., Jagodnik, K. M., Lachmann, A., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw377 · Cited by 10,799
Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool
Chen, E. Y., Tan, C. M., Kou, Y., Duan, Q., Wang, Z., Meirelles, G. V., Clark, N. R., & Ma’ayan, A. (2013) · BMC Bioinformatics · doi:10.1186/1471-2105-14-128 · Cited by 7,814
Glucose clamp technique: a method for quantifying insulin secretion and resistance.
DeFronzo, R. A., Tobin, J. D., & Andres, R. (1979) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1979.237.3.e214 · Cited by 7,425
Full-length RNA-seq from single cells using Smart-seq2
Picelli, S., Faridani, O. R., Björklund, Å. K., Winberg, G., Sagasser, S., & Sandberg, R. (2014) · Nature Protocols · doi:10.1038/nprot.2014.006 · Cited by 4,137
Elias, J. E., & Gygi, S. P. (2007) · Nature Methods · doi:10.1038/nmeth1019 · Cited by 3,925
Self-citationGOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists
Eden, E., Navon, R., Steinfeld, I., Lipson, D., & Yakhini, Z. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-48 · Cited by 3,356
Mitochondrial TCA cycle metabolites control physiology and disease
Martínez-Reyes, I., & Chandel, N. S. (2020) · Nature Communications · doi:10.1038/s41467-019-13668-3 · Cited by 2,813
(2012) · doi:10.1016/j.jmoldx.2011.08.002 · Cited by 2,567
iDISCO: A Simple, Rapid Method to Immunolabel Large Tissue Samples for Volume Imaging
Renier, N., Wu, Z., Simon, D. J., Yang, J. H., Ariel, P., & Tessier‐Lavigne, M. (2014) · Cell · doi:10.1016/j.cell.2014.10.010 · Cited by 1,856
Flagged first, then by citations
Cited by
Sorted by citations
Regulation and function of the mammalian tricarboxylic acid cycle
Arnold, P. K., & Finley, L. W. S. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102838 · Cited by 535
Metabolites as signalling molecules
Baker, S. A., & Rutter, J. P. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00572-w · Cited by 398
Elia, I., Rowe, J. H., Johnson, S. E., Joshi, S., Notarangelo, G., Kurmi, K., Weiss, S. A., Freeman, G. J., Sharpe, A. H., & Haigis, M. C. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.06.008 · Cited by 362
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
An exercise-inducible metabolite that suppresses feeding and obesity
Li, V. L., He, Y., Contrepois, K., Liu, H., Kim, J. T., Wiggenhorn, A. L., Tanzo, J. T., Tung, A. S.-H., Lyu, X., Zushin, P.-J. H., et al. (2022) · Nature · doi:10.1038/s41586-022-04828-5 · Cited by 331
Metadata
- Authors
- Reddy, A., Bozi, L. H. M., Yaghi, O. K., Mills, E. L., Xiao, H., Nicholson, H. E., Paschini, M., Paulo, J. A., Garrity, R., Laznik-Bogoslavski, D., Ferreira, J. C. B., Carl, C. S., Sjøberg, K. A., Wojtaszewski, J. F. P., Jeppesen, J. F., Kiens, B., Gygi, S. P., Richter, E. A., Mathis, D., & Chouchani, E. T.
- Affiliations
- Harvard University (US)
- Boston Children's Hospital (US)
- Dana-Farber Cancer Institute (US)
- Universidade de São Paulo (BR)
- University of Copenhagen (DK)
- Novo Nordisk (Denmark) (DK)
- Corresponding author
- Chouchani, Edward T.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-10
- Volume
- 183
- Issue
- 1
- Pages
- 62-75.e17
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7778787
- OpenAlex
- W3086698680
- Cited by
- 279
- References
- 82
- Citations by year
- 2026: 38 · 2025: 58 · 2024: 63 · 2023: 44 · 2022: 41 · 2021: 33 · 2020: 2
- FWCI
- 9.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- skeletal muscle remodeling, intracellular pH, protonation, MCT1, SUCNR1, paracrine signaling, muscle innervation, extracellular matrix remodeling, muscle strength, exercise training, mitochondrial metabolites
- MeSH terms
- Monocarboxylate Transport Protein 1, Animals, Humans, Hydrogen-Ion Concentration, Inflammation, Mitochondria, Muscle Contraction, Succinates, Signal Transduction, Muscle, Skeletal, Succinic Acid, Monocarboxylic Acid Transporters, Symporters, Receptors, G-Protein-Coupled, Mice
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
