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Home / Equine Research Bank / PLoS One / Pathways of calcium regulation, electron transport, and mito...
PloS one2021; 16(2); e0244556; doi: 10.1371/journal.pone.0244556

Pathways of calcium regulation, electron transport, and mitochondrial protein translation are molecular signatures of susceptibility to recurrent exertional rhabdomyolysis in Thoroughbred racehorses.

Abstract: Recurrent exertional rhabdomyolysis (RER) is a chronic muscle disorder of unknown etiology in racehorses. A potential role of intramuscular calcium (Ca2+) dysregulation in RER has led to the use of dantrolene to prevent episodes of rhabdomyolysis. We examined differentially expressed proteins (DEP) and gene transcripts (DEG) in gluteal muscle of Thoroughbred race-trained mares after exercise among three groups of 5 horses each; 1) horses susceptible to, but not currently experiencing rhabdomyolysis, 2) healthy horses with no history of RER (control), 3) RER-susceptible horses treated with dantrolene pre-exercise (RER-D). Tandem mass tag LC/MS/MS quantitative proteomics and RNA-seq analysis (FDR <0.05) was followed by gene ontology (GO) and semantic similarity of enrichment terms. Of the 375 proteins expressed, 125 were DEP in RER-susceptible versus control, with 52 ↑DEP mainly involving Ca2+ regulation (N = 11) (e.g. RYR1, calmodulin, calsequestrin, calpain), protein degradation (N = 6), antioxidants (N = 4), plasma membranes (N = 3), glyco(geno)lysis (N = 3) and 21 DEP being blood-borne. ↓DEP (N = 73) were largely mitochondrial (N = 45) impacting the electron transport system (28), enzymes (6), heat shock proteins (4), and contractile proteins (12) including Ca2+ binding proteins. There were 812 DEG in RER-susceptible versus control involving the electron transfer system, the mitochondrial transcription/translational response and notably the pro-apoptotic Ca2+-activated mitochondrial membrane transition pore (SLC25A27, BAX, ATP5 subunits). Upregulated mitochondrial DEG frequently had downregulation of their encoded DEP with semantic similarities highlighting signaling mechanisms regulating mitochondrial protein translation. RER-susceptible horses treated with dantrolene, which slows sarcoplasmic reticulum Ca2+ release, showed no DEG compared to control horses. We conclude that RER-susceptibility is associated with alterations in proteins, genes and pathways impacting myoplasmic Ca2+ regulation, the mitochondrion and protein degradation with opposing effects on mitochondrial transcriptional/translational responses and mitochondrial protein content. RER could potentially arise from excessive sarcoplasmic reticulum Ca2+ release and subsequent mitochondrial buffering of excessive myoplasmic Ca2+.
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Publication Date: 2021-02-10 PubMed ID: 33566847PubMed Central: PMC7875397DOI: 10.1371/journal.pone.0244556Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research presents a study on Thoroughbred racehorses, exploring the molecular mechanisms behind their susceptibility to recurrent exertional rhabdomyolysis (RER), a chronic muscle disorder. The study analysed the proteins and gene transcripts expressed in horse muscle post-exercise. The findings suggest that RER susceptibility relates to alterations in specific proteins, genes, and pathways connected to calcium regulation, protein degradation, and the function of mitochondria.

Analysis Protocol

  • The research focuses on the role of calcium (Ca2+) dysregulation in muscle cells, with the prior use of dantrolene – a muscle relaxant – to prevent rhabdomyolysis episodes influencing this focus.
  • Three groups of Thoroughbred race-trained mares were studied, five in each group. These included horses susceptible to rhabdomyolysis but not currently experiencing it, healthy horses with no RER history and RER-susceptible horses treated with dantrolene pre-exercise.
  • Using quantitative proteomics and RNA sequencing analysis, the study identified differentially expressed proteins (DEP) and gene transcripts (DEG) in the horses’ gluteal muscle after exercise.

Findings and Conclusions

  • The researchers identified 125 DEP in RER-susceptible versus control horses, notably those associated with calcium regulation and protein degradation. The altered expression of certain blood-borne proteins was also noted.
  • Decreased expression was found in mitochondrial proteins, affecting elements of the electron transport system and enzymes, among others. This process corresponds with the decrease in calcium binding proteins, which again points towards calcium dysregulation as a significant factor.
  • The team identified numerous DEG in RER-susceptible versus control horses, involving the electron transfer system, mitochondrial transcription/translational response and factors associated with the mitochondrial membrane transition pore activated by calcium.
  • Notably, the research suggests that horses treated with dantrolene, which slows the release of calcium from the sarcoplasmic reticulum, show no gene expression differences compared to control horses. This finding further cements the significance of calcium regulation in RER susceptibility.
  • Overall, the researchers have concluded that RER susceptibility in racehorses links to changes in proteins, genes, and pathways governing myoplasmic calcium regulation, mitochondrial function and protein degradation. The suggestion is the disorder could potentially arise from excessive calcium release from the sarcoplasmic reticulum and subsequent over-buffering of myoplasmic calcium by mitochondria.

Cite This Article

APA
Aldrich K, Velez-Irizarry D, Fenger C, Schott M, Valberg SJ. (2021). Pathways of calcium regulation, electron transport, and mitochondrial protein translation are molecular signatures of susceptibility to recurrent exertional rhabdomyolysis in Thoroughbred racehorses. PLoS One, 16(2), e0244556. https://doi.org/10.1371/journal.pone.0244556

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 16
Issue: 2
Pages: e0244556

Researcher Affiliations

Aldrich, Kennedy
  • Mary Anne McPhail Equine Performance Center, Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, United States of America.
Velez-Irizarry, Deborah
  • Mary Anne McPhail Equine Performance Center, Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, United States of America.
Fenger, Clara
  • Equine Integrated Medicine, PLC, Lexington, KY, United States of America.
Schott, Melissa
  • Mary Anne McPhail Equine Performance Center, Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, United States of America.
Valberg, Stephanie J
  • Mary Anne McPhail Equine Performance Center, Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, United States of America.

MeSH Terms

  • Animals
  • Calcium / metabolism
  • Dantrolene / pharmacology
  • Disease Susceptibility / metabolism
  • Electron Transport / physiology
  • Female
  • Genetic Predisposition to Disease / genetics
  • Horse Diseases / metabolism
  • Horses / metabolism
  • Mitochondria / metabolism
  • Mitochondrial Proteins / metabolism
  • Muscle, Skeletal / metabolism
  • Physical Exertion
  • Rhabdomyolysis / metabolism
  • Rhabdomyolysis / physiopathology
  • Tandem Mass Spectrometry / methods

Grant Funding

  • T32 OD011167 / NIH HHS

Conflict of Interest Statement

One of the authors (CF) is a practicing veterinarian and owner of the business Equine Integrated Medicine PLC. There are no other relevant declarations relating to employment, consultancy, patents, products in development, or marketed products. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

References

This article includes 64 references
  1. MacLeay JM, Sorum SA, Valberg SJ, Marsh WE, Sorum MD. Epidemiologic analysis of factors influencing exertional rhabdomyolysis in Thoroughbreds.. Am J Vet Res 1999;60(12):1562–6.
    pubmed: 10622169
  2. McGowan CM, Fordham T, Christley RM. Incidence and risk factors for exertional rhabdomyolysis in thoroughbred racehorses in the United Kingdom.. Vet Rec 2002;151(21):623–6.
    doi: 10.1136/vr.151.21.623pubmed: 12479297google scholar: lookup
  3. MacLeay JM, Valberg SJ, Sorum SA, Sorum MD, Kassube T, Santschi EM. Heritability of recurrent exertional rhabdomyolysis in Thoroughbred racehorses.. Am J Vet Res 1999;60(2):250–6.
    pubmed: 10048561
  4. MacLeay JM, Valberg SJ, Pagan JD, de laCorte F, Roberts J, Billstrom J. Effect of diet on thoroughbred horses with recurrent exertional rhabdomyolysis performing a standardised exercise test.. Equine Vet J Suppl 1999(30):458–62.
    doi: 10.1111/j.2042-3306.1999.tb05265.xpubmed: 10659299google scholar: lookup
  5. Fritz KL, McCue ME, Valberg SJ, Rendahl AK, Mickelson JR. Genetic mapping of recurrent exertional rhabdomyolysis in a population of North American Thoroughbreds.. Anim Genet 2012;43(6):730–8.
    doi: 10.1111/j.1365-2052.2012.02351.xpmc: PMC3665002pubmed: 22497487google scholar: lookup
  6. Tozaki T, Hirota K, Sugita S, Ishida N, Miyake T, Oki H. A genome-wide scan for tying-up syndrome in Japanese Thoroughbreds.. Anim Genet 2010;41 Suppl 2:80–6.
    doi: 10.1111/j.1365-2052.2010.02112.xpubmed: 21070280google scholar: lookup
  7. Norton EM, Mickelson JR, Binns MM, Blott SC, Caputo P, Isgren CM. Heritability of Recurrent Exertional Rhabdomyolysis in Standardbred and Thoroughbred Racehorses Derived From SNP Genotyping Data.. J Hered 2016;107(6):537–43.
    doi: 10.1093/jhered/esw042pmc: PMC5006745pubmed: 27489252google scholar: lookup
  8. Lentz LR, Valberg SJ, Balog EM, Mickelson JR, Gallant EM. Abnormal regulation of muscle contraction in horses with recurrent exertional rhabdomyolysis.. Am J Vet Res 1999;60(8):992–9.
    pubmed: 10451211
  9. Beech J, Lindborg S, Fletcher JE, Lizzo F, Tripolitis L, Braund K. Caffeine contractures, twitch characteristics and the threshold for Ca(2+)-induced Ca2+ release in skeletal muscle from horses with chronic intermittent rhabdomyolysis.. Res Vet Sci 1993;54(1):110–7.
    doi: 10.1016/0034-5288(93)90019-cpubmed: 8434138google scholar: lookup
  10. Barrey E, Jayr L, Mucher E, Gospodnetic S, Joly F, Benech P. Transcriptome analysis of muscle in horses suffering from recurrent exertional rhabdomyolysis revealed energetic pathway alterations and disruption in the cytosolic calcium regulation.. Anim Genet 2012;43(3):271–81.
    doi: 10.1111/j.1365-2052.2011.02246.xpubmed: 22486498google scholar: lookup
  11. Lentz LR, Valberg SJ, Herold LV, Onan GW, Mickelson JR, Gallant EM. Myoplasmic calcium regulation in myotubes from horses with recurrent exertional rhabdomyolysis.. Am J Vet Res 2002;63(12):1724–31.
    doi: 10.2460/ajvr.2002.63.1724pubmed: 12492289google scholar: lookup
  12. Lopez JR, Linares N, Cordovez G, Terzic A. Elevated myoplasmic calcium in exercise-induced equine rhabdomyolysis.. Pflugers Arch 1995;430(2):293–5.
    doi: 10.1007/BF00374661pubmed: 7675639google scholar: lookup
  13. Fruen BR, Mickelson JR, Louis CF. Dantrolene inhibition of sarcoplasmic reticulum Ca2+ release by direct and specific action at skeletal muscle ryanodine receptors.. J Biol Chem 1997;272(43):26965–71.
    doi: 10.1074/jbc.272.43.26965pubmed: 9341133google scholar: lookup
  14. McKenzie EC, Valberg SJ, Godden SM. Effect of oral administration of dantrolene sodium on serum creatine kinase activity after exercise in horses with recurrent exertional rhabdomyolysis.. Am J Vet Res 2004;65:74–79.
    doi: 10.2460/ajvr.2004.65.74pubmed: 14719706google scholar: lookup
  15. Edwards JG, Newtont JR, Ramzan PH, Pilsworth RC, Shepherd MC. The efficacy of dantrolene sodium in controlling exertional rhabdomyolysis in the Thoroughbred racehorse.. Equine Vet J 2003;35(7):707–11.
    doi: 10.2746/042516403775696221pubmed: 14649364google scholar: lookup
  16. McKenzie EC, Di Concetto S, Payton ME, Mandsager RE, Arko M. Effect of dantrolene premedication on various cardiovascular and biochemical variables and the recovery in healthy isoflurane-anesthetized horses.. Am J Vet Res 2015;76(4):293–301.
    doi: 10.2460/ajvr.76.4.293pubmed: 25815570google scholar: lookup
  17. Houben R, Leleu C, Fraipont A, Serteyn D, Votion DM. Determination of muscle mitochondrial respiratory capacity in Standardbred racehorses as an aid to predicting exertional rhabdomyolysis.. Mitochondrion 2015;24:99–104.
    doi: 10.1016/j.mito.2015.07.006pubmed: 26219220google scholar: lookup
  18. Valberg SJ, Perumbakkam S, McKenzie EC, Finno CJ. Proteome and transcriptome profiling of equine myofibrillar myopathy identifies diminished peroxiredoxin 6 and altered cysteine metabolic pathways.. Physiol Genomics 2018;50(12):1036–50.
    doi: 10.1152/physiolgenomics.00044.2018pmc: PMC6337024pubmed: 30289745google scholar: lookup
  19. Lindholm A, Piehl K. Fibre composition, enzyme activity and concentrations of metabolites and electrolytes in muscles of standardbred horses.. Acta Vet Scand 1974;15(3):287–309.
    pmc: PMC8407315pubmed: 4137664
  20. Cumming WJKF J.J., Hudgson P., Mahon M. Color Atlas of Muscle Pathology.. London UK: Mosby-Wolfe; 1994.
  21. Williams ZJ, Velez-Irizarry D, Petersen JL, Ochala J, Finno CJ, Valberg SJ. Candidate gene expression and coding sequence variants in Warmblood horses with myofibrillar myopathy.. Equine Vet J 2020.
    doi: 10.1111/evj.13286pmc: PMC7864122pubmed: 32453872google scholar: lookup
  22. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N. The Sequence Alignment/Map format and SAMtools.. Bioinformatics 2009;25(16):2078–9.
    doi: 10.1093/bioinformatics/btp352pmc: PMC2723002pubmed: 19505943google scholar: lookup
  23. Anders S, Pyl PT, Huber W. HTSeq—a Python framework to work with high-throughput sequencing data.. Bioinformatics 2015;31(2):166–9.
    doi: 10.1093/bioinformatics/btu638pmc: PMC4287950pubmed: 25260700google scholar: lookup
  24. Robinson MD, Oshlack A. A scaling normalization method for differential expression analysis of RNA-seq data.. Genome Biology 2010;11(3).
    doi: 10.1186/gb-2010-11-3-r25pmc: PMC2864565pubmed: 20196867google scholar: lookup
  25. Law CW, Chen Y, Shi W, Smyth GK. voom: Precision weights unlock linear model analysis tools for RNA-seq read counts.. Genome Biol 2014;15(2):R29.
    doi: 10.1186/gb-2014-15-2-r29pmc: PMC4053721pubmed: 24485249google scholar: lookup
  26. Liu R, Holik AZ, Su S, Jansz N, Chen K, Leong HS. Why weight? Modelling sample and observational level variability improves power in RNA-seq analyses.. Nucleic Acids Res 2015;43(15):e97.
    doi: 10.1093/nar/gkv412pmc: PMC4551905pubmed: 25925576google scholar: lookup
  27. Vu VM, B., Hester, J., Held, M.. Github repository.. .
  28. Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data.. Bioinformatics 2010;26(1):139–40.
    doi: 10.1093/bioinformatics/btp616pmc: PMC2796818pubmed: 19910308google scholar: lookup
  29. McCarthy DJ, Chen Y, Smyth GK. Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation.. Nucleic Acids Res 2012;40(10):4288–97.
    doi: 10.1093/nar/gks042pmc: PMC3378882pubmed: 22287627google scholar: lookup
  30. McCarthy DJ, Smyth GK. Testing significance relative to a fold-change threshold is a TREAT.. Bioinformatics 2009;25(6):765–71.
    doi: 10.1093/bioinformatics/btp053pmc: PMC2654802pubmed: 19176553google scholar: lookup
  31. Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters.. OMICS 2012;16(5):284–7.
    doi: 10.1089/omi.2011.0118pmc: PMC3339379pubmed: 22455463google scholar: lookup
  32. Yu G, Wang LG, Yan GR, He QY. DOSE: an R/Bioconductor package for disease ontology semantic and enrichment analysis.. Bioinformatics 2015;31(4):608–9.
    doi: 10.1093/bioinformatics/btu684pubmed: 25677125google scholar: lookup
  33. Jiang J, J., Conrath, D.W.. Semantic similarity based on corpus statistics and lexical taxonomy.. 10th International research conference on computational linguistics; 1997; Taipei, Taiwan: The Association for Computational Linguistics and Chinese Language Processing (ACLCLP).
  34. Yu G, Li F, Qin Y, Bo X, Wu Y, Wang S. GOSemSim: an R package for measuring semantic similarity among GO terms and gene products.. Bioinformatics 2010;26(7):976–8.
    doi: 10.1093/bioinformatics/btq064pubmed: 20179076google scholar: lookup
  35. Chatfield KC, Coughlin CR 2nd, Friederich MW, Gallagher RC, Hesselberth JR, Lovell MA. Mitochondrial energy failure in HSD10 disease is due to defective mtDNA transcript processing.. Mitochondrion 2015;21:1–10.
    doi: 10.1016/j.mito.2014.12.005pmc: PMC4355277pubmed: 25575635google scholar: lookup
  36. Li Y, Dudek J, Guiard B, Pfanner N, Rehling P, Voos W. The presequence translocase-associated protein import motor of mitochondria. Pam16 functions in an antagonistic manner to Pam18.. J Biol Chem 2004;279(36):38047–54.
    doi: 10.1074/jbc.M404319200pubmed: 15218029google scholar: lookup
  37. Smirnov A, Comte C, Mager-Heckel AM, Addis V, Krasheninnikov IA, Martin RP. Mitochondrial Enzyme Rhodanese Is Essential for 5 S Ribosomal RNA Import into Human Mitochondria.. Journal of Biological Chemistry 2010;285(40):30792–803.
    doi: 10.1074/jbc.M110.151183pmc: PMC2945573pubmed: 20663881google scholar: lookup
  38. Gehlert S, Bloch W, Suhr F. Ca2+-dependent regulations and signaling in skeletal muscle: from electro-mechanical coupling to adaptation.. Int J Mol Sci 2015;16(1):1066–95.
    doi: 10.3390/ijms16011066pmc: PMC4307291pubmed: 25569087google scholar: lookup
  39. Kwong JQ, Molkentin JD. Physiological and pathological roles of the mitochondrial permeability transition pore in the heart.. Cell Metab 2015;21(2):206–14.
    doi: 10.1016/j.cmet.2014.12.001pmc: PMC4616258pubmed: 25651175google scholar: lookup
  40. Westerblad H, Allen DG. Changes of myoplasmic calcium concentration during fatigue in single mouse muscle fibers.. J Gen Physiol 1991;98(3):615–35.
    doi: 10.1085/jgp.98.3.615pmc: PMC2229059pubmed: 1761971google scholar: lookup
  41. Schiaffino S, Reggiani C. Fiber types in mammalian skeletal muscles.. Physiol Rev 2011;91(4):1447–531.
    doi: 10.1152/physrev.00031.2010pubmed: 22013216google scholar: lookup
  42. Terentyev D, Viatchenko-Karpinski S, Gyorke I, Volpe P, Williams SC, Gyorke S. Calsequestrin determines the functional size and stability of cardiac intracellular calcium stores: Mechanism for hereditary arrhythmia.. Proc Natl Acad Sci U S A 2003;100(20):11759–64.
    doi: 10.1073/pnas.1932318100pmc: PMC208831pubmed: 13130076google scholar: lookup
  43. Isgren CM, Upjohn MM, Fernandez-Fuente M, Massey C, Pollott G, Verheyen KL. Epidemiology of exertional rhabdomyolysis susceptibility in standardbred horses reveals associated risk factors and underlying enhanced performance.. PLoS One 2010;5(7):e11594.
    doi: 10.1371/journal.pone.0011594pmc: PMC2904368pubmed: 20644724google scholar: lookup
  44. Giulivi C, Ross-Inta C, Omanska-Klusek A, Napoli E, Sakaguchi D, Barrientos G. Basal bioenergetic abnormalities in skeletal muscle from ryanodine receptor malignant hyperthermia-susceptible R163C knock-in mice.. J Biol Chem 2011;286(1):99–113.
    doi: 10.1074/jbc.M110.153247pmc: PMC3013050pubmed: 20978128google scholar: lookup
  45. Tripathy A, Xu L, Mann G, Meissner G. Calmodulin activation and inhibition of skeletal muscle Ca2+ release channel (ryanodine receptor).. Biophys J 1995;69(1):106–19.
    doi: 10.1016/S0006-3495(95)79880-0pmc: PMC1236229pubmed: 7669888google scholar: lookup
  46. Beard NA, Casarotto MG, Wei L, Varsanyi M, Laver DR, Dulhunty AF. Regulation of ryanodine receptors by calsequestrin: effect of high luminal Ca2+ and phosphorylation.. Biophys J 2005;88(5):3444–54.
    doi: 10.1529/biophysj.104.051441pmc: PMC1305491pubmed: 15731387google scholar: lookup
  47. Anyatonwu GI, Ehrlich BE. Calcium signaling and polycystin-2.. Biochem Biophys Res Commun 2004;322(4):1364–73.
    doi: 10.1016/j.bbrc.2004.08.043pubmed: 15336985google scholar: lookup
  48. Wetzel P, Kleinke T, Papadopoulos S, Gros G. Inhibition of muscle carbonic anhydrase slows the Ca(2+) transient in rat skeletal muscle fibers.. Am J Physiol Cell Physiol 2002;283(4):C1242–53.
    doi: 10.1152/ajpcell.00106.2002pubmed: 12225987google scholar: lookup
  49. Nishita T, Ohohashi T, Asari M. Determination of carbonic anhydrase III isoenzyme concentration in sera of racehorses with exertional rhabdomyolysis.. Am J Vet Res 1995;56(2):162–6.
    pubmed: 7717578
  50. Dranchak PK, Valberg SJ, Onan GW, Gallant EM, Binns MM, Swinburne JE. Exclusion of linkage of the RYR1, CACNA1S, and ATP2A1 genes to recurrent exertional rhabdomyolysis in Thoroughbreds.. Am J Vet Res 2006;67(8):1395–400.
    doi: 10.2460/ajvr.67.8.1395pubmed: 16881852google scholar: lookup
  51. Bellinger AM, Mongillo M, Marks AR. Stressed out: the skeletal muscle ryanodine receptor as a target of stress.. J Clin Invest 2008;118(2):445–53.
    doi: 10.1172/JCI34006pmc: PMC2214709pubmed: 18246195google scholar: lookup
  52. Andersson DC, Betzenhauser MJ, Reiken S, Umanskaya A, Shiomi T, Marks AR. Stress-induced increase in skeletal muscle force requires protein kinase A phosphorylation of the ryanodine receptor.. J Physiol 2012;590(24):6381–7.
    doi: 10.1113/jphysiol.2012.237925pmc: PMC3533199pubmed: 23070698google scholar: lookup
  53. Nogueira GP, Barnabe RC. Is the Thoroughbred race-horse under chronic stress?. Braz J Med Biol Res 1997;30(10):1237–9.
    doi: 10.1590/s0100-879x1997001000016pubmed: 9496444google scholar: lookup
  54. Williams GS, Boyman L, Chikando AC, Khairallah RJ, Lederer WJ. Mitochondrial calcium uptake.. Proc Natl Acad Sci U S A 2013;110(26):10479–86.
    doi: 10.1073/pnas.1300410110pmc: PMC3696793pubmed: 23759742google scholar: lookup
  55. Eisner V, Csordas G, Hajnoczky G. Interactions between sarco-endoplasmic reticulum and mitochondria in cardiac and skeletal muscle—pivotal roles in Ca(2)(+) and reactive oxygen species signaling.. J Cell Sci 2013;126(Pt 14):2965–78.
    pmc: PMC3711195pubmed: 23843617
  56. Shoshan-Barmatz V, De S, Meir A. The Mitochondrial Voltage-Dependent Anion Channel 1, Ca(2+) Transport, Apoptosis, and Their Regulation.. Front Oncol 2017;7:60.
    doi: 10.3389/fonc.2017.00060pmc: PMC5385329pubmed: 28443244google scholar: lookup
  57. Lemasters JJ, Theruvath TP, Zhong Z, Nieminen AL. Mitochondrial calcium and the permeability transition in cell death.. Biochim Biophys Acta 2009;1787(11):1395–401.
    doi: 10.1016/j.bbabio.2009.06.009pmc: PMC2730424pubmed: 19576166google scholar: lookup
  58. Karch J, Molkentin JD. Identifying the components of the elusive mitochondrial permeability transition pore.. Proc Natl Acad Sci U S A 2014;111(29):10396–7.
    doi: 10.1073/pnas.1410104111pmc: PMC4115577pubmed: 25002521google scholar: lookup
  59. Fernstrom M, Tonkonogi M, Sahlin K. Effects of acute and chronic endurance exercise on mitochondrial uncoupling in human skeletal muscle.. J Physiol 2004;554(Pt 3):755–63.
    doi: 10.1113/jphysiol.2003.055202pmc: PMC1664806pubmed: 14634202google scholar: lookup
  60. Scholte HR, Verduin MH, Ross JD, Van den Hoven R, Wensing T, Breuking HJ. Equine exertional rhabdomyolysis: activity of the mitochondrial respiratory chain and the carnitine system in skeletal muscle [see comment].. Equine Vet J 1991;23(2):142–4.
    doi: 10.1111/j.2042-3306.1991.tb02740.xpubmed: 2044508google scholar: lookup
  61. MacLeay JM, Valberg SJ, Pagan JD, Xue JL, De La Corte FD, Roberts J. Effect of ration and exercise on plasma creatine kinase activity and lactate concentration in Thoroughbred horses with recurrent exertional rhabdomyolysis.. Am J Vet Res 2000;61(11):1390–5.
    doi: 10.2460/ajvr.2000.61.1390pubmed: 11108185google scholar: lookup
  62. Blazquez L, Emmett W, Faraway R, Pineda JMB, Bajew S, Gohr A. Exon Junction Complex Shapes the Transcriptome by Repressing Recursive Splicing.. Mol Cell 2018;72(3):496–509 e9.
    doi: 10.1016/j.molcel.2018.09.033pmc: PMC6224609pubmed: 30388411google scholar: lookup
  63. Meijer HA, Kong YW, Lu WT, Wilczynska A, Spriggs RV, Robinson SW. Translational repression and eIF4A2 activity are critical for microRNA-mediated gene regulation.. Science 2013;340(6128):82–5.
    doi: 10.1126/science.1231197pubmed: 23559250google scholar: lookup
  64. Lecker SH, Jagoe RT, Gilbert A, Gomes M, Baracos V, Bailey J. Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression.. FASEB J 2004;18(1):39–51.
    doi: 10.1096/fj.03-0610compubmed: 14718385google scholar: lookup
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