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Disruption of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Integrity Contributes to Muscle Insulin Resistance in Mice and Humans
Abstract
Modifications of the interactions between endoplasmic reticulum (ER) and mitochondria, defined as mitochondria-associated membranes (MAMs), were recently shown to be involved in the control of hepatic insulin action and glucose homeostasis, but with conflicting results. Whereas skeletal muscle is the primary site of insulin-mediated glucose uptake and the main target for alterations in insulin-resistant states, the relevance of MAM integrity in muscle insulin resistance is unknown. Deciphering the importance of MAMs on muscle insulin signaling could help to clarify this controversy. Here, we show in skeletal muscle of different mice models of obesity and type 2 diabetes (T2D) a marked disruption of ER-mitochondria interactions as an early event preceding mitochondrial dysfunction and insulin resistance. Furthermore, in human myotubes, palmitate-induced insulin resistance is associated with a reduction of structural and functional ER-mitochondria interactions. Importantly, experimental increase of ER-mitochondria contacts in human myotubes prevents palmitate-induced alterations of insulin signaling and action, whereas disruption of MAM integrity alters the action of the hormone. Lastly, we found an association between altered insulin signaling and ER-mitochondria interactions in human myotubes from obese subjects with or without T2D compared with healthy lean subjects. Collectively, our data reveal a new role of MAM integrity in insulin action of skeletal muscle and highlight MAM disruption as an essential subcellular alteration associated with muscle insulin resistance in mice and humans. Therefore, reduced ER-mitochondria coupling could be a common alteration of several insulin-sensitive tissues playing a key role in altered glucose homeostasis in the context of obesity and T2D.
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“Particularly, the dysregulation of the interactions between mitochondria and the ER has been reported to be implicated in the pathogenesis of insulin resistance (Flamment et al., 2012; Sebastian et al., 2012; Tubbs et al., 2018).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Tubbs et al., 2018
In the citing paper
“Remarkably, the interaction between mitochondria and the sarcoplasmic reticulum (SR) has been confirmed in skeletal muscle (Tubbs et al., 2018; Thoudam et al., 2019).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Tubbs et al., 2018
In the citing paper
“Not surprisingly, also in consideration of the pivotal role of skeletal muscle in the regulation of glucose homeostasis, the dysregulation of MAMs may contribute to skeletal muscle insulin resistance in mice and humans (Tubbs et al., 2018; Thoudam et al., 2019).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Tubbs et al., 2018
In the citing paper
“Mitochondria-SR interactions have been reported to be reduced in the skeletal muscle of high-fat or genetically induced obese and diabetic mice as well as in human primary myotubes treated with palmitic acid (Tubbs et al., 2018)”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Tubbs et al., 2018
In the citing paper
“indicating that the MAM reduction may represent a link between mitochondrial dysfunction and insulin resistance in skeletal muscle.”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Tubbs et al., 2018
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Cites
Krssak, M., Falk Petersen, K., Dresner, A., DiPietro, L., Vogel, S. M., Rothman, D. L., Shulman, G. I., & Roden, M. (1999) · Diabetologia · doi:10.1007/s001250051123 · Cited by 1,264
Cárdenas, C., Miller, R. A., Smith, I., Bui, T., Molgó, J., Müller, M., Vais, H., Cheung, K.-H., Yang, J., Parker, I., et al. (2010) · Cell · doi:10.1016/j.cell.2010.06.007 · Cited by 1,026
Endoplasmic reticulum-mitochondria contacts: Function of the junction
Rowland, A. A., & Voeltz, G. K. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3440 · Cited by 1,018 · cited 1×
“Indeed, mitochondria and ER interact at contact points, called mitochondria-associated ER membranes (MAMs), to exchange calcium (Ca) and lipids, thus regulating cell metabolism and fate (4,5).”
BackgroundRegulation of mitochondrial ATP synthesis by calcium: Evidence for a long-term metabolic priming
Jouaville, L. S., Pinton, P., Bastianutto, C., Rutter, G. A., & Rizzuto, R. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.24.13807 · Cited by 831
Bonnard, C., Durand, A., Peyrol, S., Chanseaume, E., Chauvin, M.-A., Morio, B., Vidal, H., & Rieusset, J. (2008) · Journal of Clinical Investigation · doi:10.1172/jci32601 · Cited by 819
Self-citationArruda, A. P., Pers, B. M., Parlakgül, G., Güney, E., Inouye, K., & Hotamışlıgil, G. S. (2014) · Nature Medicine · doi:10.1038/nm.3735 · Cited by 741
Sebastián, D., Hernández-Alvarez, M. I., Segalés, J., Sorianello, E., Muñoz, J. P., Sala, D., Waget, A., Liesa, M., Paz, J. C., Gopalacharyulu, P., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1108220109 · Cited by 673
The role of mitochondria in the pathogenesis of type 2 diabetes
Patti, M.-E., & Corvera, S. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0027 · Cited by 551
Betz, C., Stracka, D., Prescianotto-Baschong, C., Frieden, M., Demaurex, N., & Hall, M. N. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1302455110 · Cited by 538
The coming of age of the mitochondria–ER contact: a matter of thickness
Giacomello, M., & Pellegrini, L. (2016) · Cell Death and Differentiation · doi:10.1038/cdd.2016.52 · Cited by 471
Mfn2 modulates the UPR and mitochondrial function via repression of PERK
Muñoz, J. P., Ivanova, S., Sánchez‐Wandelmer, J., Martínez‐Cristóbal, P., Noguera, E., Sancho, A., Díaz‐Ramos, A., Hernández‐Alvarez, M. I., Sebastián, D., Mauvezin, C., et al. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.168 · Cited by 451
Tubbs, E., Theurey, P., Vial, G., Bendridi, N., Bravard, A., Chauvin, M.-A., Ji-Cao, J., Zoulim, F., Bartosch, B., Ovize, M., et al. (2014) · Diabetes · doi:10.2337/db13-1751 · Cited by 411 · cited 10×
“Transmission Electron Microscope Analysis Fixation and posttreatment of muscle fractions or myotubes and the observation of ultrathin sections were performed as previously described (6).”
BackgroundMethodInfluentialSelf-citationNew insights into ER stress-induced insulin resistance
Flamment, M., Hajduch, E., Ferré, P., & Foufelle, F. (2012) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.06.003 · Cited by 306
Bouzakri, K., Roques, M., Gual, P., Espinosa, S., Guebre-Egziabher, F., Riou, J.-P., Laville, M., Le Marchand-Brustel, Y., Tanti, J.-F., & Vidal, H. (2003) · Diabetes · doi:10.2337/diabetes.52.6.1319 · Cited by 305
Self-citationRegulation by Insulin of Gene Expression in Human Skeletal Muscle and Adipose Tissue
Ducluzeau, P., Peretti, N., Laville, M., Andréelli, F., Véga, N., Riou, J. P., & Vidal, H. (2001) · Diabetes · doi:10.2337/diabetes.50.5.1134 · Cited by 263
Self-citationCieri, D., Vicario, M., Giacomello, M., Vallese, F., Filadi, R., Wagner, T., Pozzan, T., Pizzo, P., Scorrano, L., Brini, M., et al. (2017) · Cell Death and Differentiation · doi:10.1038/s41418-017-0033-z · Cited by 255
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
Eisner, V., Csordás, G., & Hajnóczky, G. (2013) · Journal of Cell Science · doi:10.1242/jcs.093609 · Cited by 219
Inositol-1,4,5-trisphosphate receptor regulates hepatic gluconeogenesis in fasting and diabetes
Wang, Y., Li, G., Goode, J., Paz, J. C., Ouyang, K., Screaton, R. A., Fischer, W. H., Chen, J., Tabas, I. A., & Montminy, M. (2012) · Nature · doi:10.1038/nature10988 · Cited by 217
Vial, G., Chauvin, M., Bendridi, N., Durand, A., Meugnier, E., Madec, A., Bernoud‐Hubac, N., de Barros, J.-P. P., Fontaine, E. M., Acquaviva, C., et al. (2014) · Diabetes · doi:10.2337/db14-1220 · Cited by 194
Self-citationRieusset, J., Fauconnier, J., Paillard, M., Belaïdi, E., Tubbs, E., Chauvin, M., Durand, A., Bravard, A., Teixeira, G., Bartosch, B., et al. (2015) · Diabetologia · doi:10.1007/s00125-015-3829-8 · Cited by 177
Self-citationTheurey, P., Tubbs, E., Vial, G., Jacquemetton, J., Bendridi, N., Chauvin, M.-A., Alam, M. R., Le Romancer, M., Vidal, H., & Rieusset, J. (2016) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjw004 · Cited by 175
Self-citationInsulin signaling and glucose transport in insulin resistant human skeletal muscle
Karlsson, H. K. R., & Zierath, J. R. (2007) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-007-0030-9 · Cited by 159
The Diabetic Phenotype Is Conserved in Myotubes Established From Diabetic Subjects
Gaster, M., Petersen, I. M., Højlund, K., Poulsen, P., & Beck‐Nielsen, H. (2002) · Diabetes · doi:10.2337/diabetes.51.4.921 · Cited by 150
Dif, N., Euthine, V., Gonnet, E., Laville, M., Vidal, H., & Lefai, É. (2006) · Biochemical Journal · doi:10.1042/bj20060499 · Cited by 148
Self-citationFATE1 antagonizes calcium‐ and drug‐induced apoptosis by uncoupling ER and mitochondria
Doghman, M., Granatiero, V., Sbiera, S., Sbiera, I., Lacas‐Gervais, S., Brau, F., Faßnacht, M., Rizzuto, R., & Lalli, E. (2016) · EMBO Reports · doi:10.15252/embr.201541504 · Cited by 148
The molecular hug between the ER and the mitochondria
Kornmann, B. (2013) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2013.02.010 · Cited by 144
Metabolic signaling functions of ER–mitochondria contact sites: role in metabolic diseases
Tubbs, E., & Rieusset, J. (2016) · Journal of Molecular Endocrinology · doi:10.1530/jme-16-0189 · Cited by 130
Self-citationWang, C., Chen, Y., Wu, C.-Y., Wu, P.-C., Huang, Y., Kao, C., Lin, C., Kao, L., Tsai, T., & Wei, Y. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu193 · Cited by 109
Perrin, L., Loizides‐Mangold, U., Skarupelova, S., Pulimeno, P., Chanon, S., Robert, M., Bouzakri, K., Modoux, C., Roux‐Lombard, P., Vidal, H., et al. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.07.009 · Cited by 107
Self-citationTransfer and Tunneling of Ca2+ from Sarcoplasmic Reticulum to Mitochondria in Skeletal Muscle
Shkryl, V. M., & Shirokova, N. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505024200 · Cited by 102
[8] Preparation and properties of complex IV (Ferrocytochrome c: Oxygen oxidoreductase EC 1.9.3.1)
Errede, B., Kamen, M. D., & Hatefi, Y. (1978) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(78)53011-5 · Cited by 99
Alteration in mitochondrial Ca 2+ uptake disrupts insulin signaling in hypertrophic cardiomyocytes
Gutiérrez, T., Parra, V., Troncoso, R., Pennanen, C., Contreras‐Ferrat, A. E., Vásquez-Trincado, C., Morales, P. E., López‐Crisosto, C., Sotomayor-Flores, C., Chiong, M., et al. (2014) · Cell Communication and Signaling · doi:10.1186/s12964-014-0068-4 · Cited by 84
Lecomte, V., Meugnier, E., Euthine, V., Durand, C., Freyssenet, D. G., Némoz, G., Rome, S., Vidal, H., & Lefai, É. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00690-09 · Cited by 84
Self-citationChaussade, C., Pirola, L., Bonnafous, S., Blondeau, F., Verca, S. B., Tronchère, H., Portis, F., Rusconi, S., Payrastre, B., Laporte, J., et al. (2003) · Molecular Endocrinology · doi:10.1210/me.2003-0261 · Cited by 82
Shinjo, S., Jiang, S. S., Nameta, M., Suzuki, T., Kanai, M., Nomura, Y., & Goda, N. (2017) · Experimental Cell Research · doi:10.1016/j.yexcr.2017.08.006 · Cited by 74
Takeshima, H., Venturi, E., & Sitsapesan, R. M. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2014.281881 · Cited by 71
Rieusset, J. (2015) · Diabetes & Metabolism · doi:10.1016/j.diabet.2015.02.006 · Cited by 69
Self-citationTubbs, E., & Rieusset, J. (2016) · Journal of Visualized Experiments · doi:10.3791/54899 · Cited by 60
Self-citationContreras‐Ferrat, A. E., Llanos, P., Vásquez-Trincado, C., Espinosa, A., Osorio‐Fuentealba, C., Arias‐Calderón, M., Lavandero, S., Klip, A., Hidalgo, C., & Jaimovich, E. (2014) · Journal of Cell Science · doi:10.1242/jcs.138982 · Cited by 56
Rieusset, J., Chauvin, M., Durand, A., Bravard, A., Laugerette, F., Michalski, M., & Vidal, H. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.11.135 · Cited by 54
Self-citationRieusset, J. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.06.097 · Cited by 47
Self-citationYe, R., Ni, M., Wang, M., Luo, S. D., Zhu, G., Chow, R. H.-P., & Lee, A. S. (2011) · Journal of Endocrinology · doi:10.1530/joe-11-0012 · Cited by 46
Henning, R. H., Duin, M., den Hertog, A., & Nelemans, A. (1993) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1993.tb13875.x · Cited by 40
Gastebois, C., Chanon, S., Rome, S., Durand, C., Pelascini, É., Jalabert, A., Euthine, V., Pialoux, V., Blanc, S., Simon, C., et al. (2016) · Physiological Reports · doi:10.14814/phy2.12902 · Cited by 19
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Pinti, M. V., Fink, G. K., Hathaway, Q. A., Durr, A. J., Kunovac, A., & Hollander, J. M. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00314.2018 · Cited by 447
Sergi, D., Naumovski, N., Heilbronn, L. K., Abeywardena, M., O’Callaghan, N., Lionetti, L., & Luscombe-Marsh, N. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00532 · Cited by 347
Rieusset, J. (2018) · Cell Death & Disease · doi:10.1038/s41419-018-0416-1 · Cited by 248
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Rosa, S. C. D. S., Nayak, N., Caymo, A. M., & Gordon, J. W. (2020) · Physiological Reports · doi:10.14814/phy2.14607 · Cited by 271
Pathak, T., & Trebak, M. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.07.001 · Cited by 227
Metadata
- Authors
- Tubbs, E., Chanon, S., Robert, M., Bendridi, N., Bidaux, G., Chauvin, M.-A., Ji-Cao, J., Durand, C., Gauvrit-Ramette, D., Vidal, H., Lefai, E., & Rieusset, J.
- Affiliations
- Lyon 1 Université (FR)
- Laboratoire de Recherche en Cardiovasculaire, Métabolisme, Diabétologie et Nutrition (CarMeN), INSERM U1060, INRA U1397, Institut National des Sciences Appliquées-Lyon, Université Claude Bernard Lyon1, Oullins, Lyon, France
- Corresponding author
- Rieusset, Jennifer
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2018-01-11
- Volume
- 67
- Issue
- 4
- Pages
- 636-650
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2783880365
- Cited by
- 202
- References
- 46
- Citations by year
- 2026: 19 · 2025: 17 · 2024: 26 · 2023: 19 · 2022: 22 · 2021: 35 · 2020: 32 · 2019: 23 · 2018: 9
- FWCI
- 8.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- INSERM
- Agence Nationale de la Recherche (ANR-09-JCJC-0116)
- Fondation pour la Recherche Médicale (DRM20101220461)
- 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 (medical) › Adipose Tissue and Metabolism
- Keywords
- mitochondria-associated endoplasmic reticulum membranes, ER-mitochondria communication, muscle insulin resistance, skeletal muscle, type 2 diabetes, obesity, palmitate, insulin signaling, mitochondrial dysfunction, glucose homeostasis, myotubes
- MeSH terms
- Aged, Animals, Diabetes Mellitus, Type 2, Disease Models, Animal, Endoplasmic Reticulum, Female, Glucose, Homeostasis, Humans, Insulin, Insulin Resistance, Intracellular Membranes, Male, Middle Aged, Mitochondria, Muscle, Obesity, Palmitates, Signal Transduction, Muscle, Skeletal, Muscle Fibers, Skeletal, Mice
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