The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Evidence for a Mitochondrial Regulatory Pathway Defined by Peroxisome Proliferator–Activated Receptor-γ Coactivator-1α, Estrogen-Related Receptor-α, and Mitofusin 2
Abstract
Mitofusin 2 (Mfn2) is a mitochondrial membrane protein that participates in mitochondrial fusion and regulates mitochondrial metabolism in mammalian cells. Here, we show that Mfn2 gene expression is induced in skeletal muscle and brown adipose tissue by conditions associated with enhanced energy expenditure, such as cold exposure or β3-adrenergic agonist treatment. In keeping with the role of peroxisome proliferator–activated receptor-γ coactivator (PGC)-1α on energy expenditure, we demonstrate a stimulatory effect of PGC-1α on Mfn2 mRNA and protein expression in muscle cells. PGC-1α also stimulated the activity of the Mfn2 promoter, which required the integrity of estrogen-related receptor-α (ERRα)-binding elements located at −413/−398. ERRα also activated the transcriptional activity of the Mfn2 promoter, and the effects were synergic with those of PGC-1α. Mfn2 loss of function reduced the stimulatory effect of PGC-1α on mitochondrial membrane potential. Exposure to cold substantially increased Mfn2 gene expression in skeletal muscle from heterozygous Mfn2 knock-out mice, which occurred in the presence of higher levels of PGC-1α mRNA compared with control mice. Our results indicate the existence of a regulatory pathway involving PGC-1α, ERRα, and Mfn2. Alterations in this regulatory pathway may participate in the pathophysiology of insulin-resistant conditions and type 2 diabetes.
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“conditions that increase energy expenditure such as cold exposure, chronic exercise or nutraceuticals as resveratrol are associated with higher Mfn2 expression in skeletal muscle and brown adipose tissue in mice and humans (Cartoni et al., 2005; Dolinsky et al., 2013; Soriano et al., 2006).”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Soriano et al., 2006
In the citing paper
“Similar to many mitochondrial genes, Mfn2 expression is controlled by PGC-1α (Soriano et al, 2006), suggesting that decreased PGC-1α activity explains the defects in Mfn2 observed in obese and T2DM individuals.”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Soriano et al, 2006
In the citing paper
“PGC-1α and its downstream target gene product, estrogen-related receptor-α (ERRα), stimulate the expression of Mfn2 (Cartoni et al., 2005; Soriano et al., 2006).”
From New insights into the role of mitochondria in aging: mitochondrial dynamics and more (2010) · cites this paper as Soriano et al., 2006
In the citing paper
“PGC-1 family members interact with the family of estrogen-related nuclear receptors, or ERRs, to transactivate transcription of oxidative genes (275) and mitofusins (276).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [276]
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Cites
Wu, Z., Puigserver, P., Andersson, U., Zhang, C., Adelmant, G., Mootha, V., Troy, A., Cinti, S., Lowell, B., Scarpulla, R. C., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80611-x · Cited by 4,139
A Cold-Inducible Coactivator of Nuclear Receptors Linked to Adaptive Thermogenesis
Puigserver, P., Wu, Z., Park, C. W., Graves, R., Wright, M., & Spiegelman, B. M. (1998) · Cell · doi:10.1016/s0092-8674(00)81410-5 · Cited by 3,864
Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1
Rodgers, J. T., Lerin, C., Haas, W., Gygi, S. P., Spiegelman, B. M., & Puigserver, P. (2005) · Nature · doi:10.1038/nature03354 · Cited by 3,160
Chen, H., Detmer, S. A., Ewald, A. J., Griffin, E. E., Fraser, S. E., & Chan, D. C. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200211046 · Cited by 2,601
Self-citationTranscriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres
Lin, J., Wu, H., Tarr, P. T., Zhang, C.-Y., Wu, Z., Boss, O., Michael, L. F., Puigserver, P., Isotani, E., Olson, E. N., et al. (2002) · Nature · doi:10.1038/nature00904 · Cited by 2,546
Puigserver, P., & Spiegelman, B. M. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0012 · Cited by 2,076
Patti, M. E., Butte, A. J., Crunkhorn, S., Cusi, K., Berria, R., Kashyap, S., Miyazaki, Y., Kohane, I., Costello, M., Saccone, R., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1032913100 · Cited by 1,952
Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1
Yoon, J. C., Puigserver, P., Chen, G., Donovan, J., Wu, Z., Rhee, J., Adelmant, G., Stafford, J., Kahn, C. R., Granner, D. K., et al. (2001) · Nature · doi:10.1038/35093050 · Cited by 1,821
Insulin-regulated hepatic gluconeogenesis through FOXO1–PGC-1α interaction
Puigserver, P., Rhee, J., Donovan, J., Walkey, C. J., Yoon, J. C., Oriente, F., Kitamura, Y., Altomonte, J., Dong, H., Accili, D., et al. (2003) · Nature · doi:10.1038/nature01667 · Cited by 1,487
CREB regulates hepatic gluconeogenesis through the coactivator PGC-1
Herzig, S., Long, F., Jhala, U. S., Hedrick, S., Quinn, R., Bauer, A., Rudolph, D., Schutz, G., Yoon, C., Puigserver, P., et al. (2001) · Nature · doi:10.1038/35093131 · Cited by 1,440
Peroxisome proliferator–activated receptor γ coactivator-1 promotes cardiac mitochondrial biogenesis
Lehman, J. J., Barger, P. M., Kovacs, A., Saffitz, J. E., Medeiros, D. M., & Kelly, D. P. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10268 · Cited by 1,285
Defects in Adaptive Energy Metabolism with CNS-Linked Hyperactivity in PGC-1α Null Mice
Lin, J., Wu, P.-H., Tarr, P. T., Lindenberg, K. S., St-Pierre, J., Zhang, C.-Y., Mootha, V. K., Jäger, S., Vianna, C. R., Reznick, R. M., et al. (2004) · Cell · doi:10.1016/j.cell.2004.09.013 · Cited by 1,162
Control of mitochondrial morphology by a human mitofusin
Santel, A., & Fuller, M. T. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.5.867 · Cited by 1,012
Mitofusin-2 Determines Mitochondrial Network Architecture and Mitochondrial Metabolism
Bach, D., Pich, S., Soriano, F. X., Vega, N., Baumgartner, B., Oriola, J., Daugaard, J. R., Lloberas, J., Camps, M., Zierath, J. R., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212754200 · Cited by 832 · cited 9×
“Mitofusin 2 (Mfn2) is a mitochondrial fusion protein (16–19) that is expressed mainly in tissues with high energetic requirements, such as skeletal muscle and heart (16); consequently, it shows an expression pattern similar to that of PGC-1 .”
BackgroundMethodInfluentialSelf-citationMootha, V. K., Handschin, C., Arlow, D., Xie, X., St. Pierre, J., Sihag, S., Yang, W., Altshuler, D., Puigserver, P., Patterson, N., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401401101 · Cited by 688
Schreiber, S., Emter, R., Hock, M. B., Knutti, D., Cardenas, J., Podvinec, M., Oakeley, E. J., & Kralli, A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308686101 · Cited by 678
Michael, L. F., Wu, Z., Cheatham, R. B., Puigserver, P., Adelmant, G., Lehman, J. J., Kelly, D. P., & Spiegelman, B. M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.061035098 · Cited by 663
Rojo, M., Legros, F., Chateau, D., & Lombès, A. (2002) · Journal of Cell Science · doi:10.1242/jcs.115.8.1663 · Cited by 555
St‐Pierre, J., Lin, J. D., Krauss, S., Tarr, P. T., Yang, R., Newgard, C. B., & Spiegelman, B. M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301850200 · Cited by 554
Schreiber, S., Knutti, D., Brogli, K., Uhlmann, T., & Kralli, A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212923200 · Cited by 458
Pich, S., Bach, D., Briones, P., Liesa, M., Camps, M., Testar, X., Palacín, M., & Zorzano, A. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi149 · Cited by 455
Self-citationMitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells
Santel, A., Frank, S., Gaume, B. R., Herrler, M., Youle, R. J., & Fuller, M. T. (2003) · Journal of Cell Science · doi:10.1242/jcs.00479 · Cited by 445
Mitofusins 1/2 and ERRα expression are increased in human skeletal muscle after physical exercise
Cartoni, R., Léger, B., Hock, M. B., Praz, M., Crettenand, A., Pich, S., Ziltener, J., Luthi, F., Dériaz, O., Zorzano, A., et al. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.092031 · Cited by 406
Self-citationSLADEK, R. M., Bader, J.-A., & Giguère, V. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.9.5400 · Cited by 375
Dysregulation of HSG triggers vascular proliferative disorders
Chen, K.-H., Guo, X., Ma, D., Guo, Y., Li, Q., Yang, D., Li, P., Qiu, X., Wen, S., Xiao, R.-P., et al. (2004) · Nature Cell Biology · doi:10.1038/ncb1161 · Cited by 370
Expression of Mfn2, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle
Bach, D., Naon, D., Pich, S., Soriano, F. X., Vega, N., Rieusset, J., Laville, M., Guillet, C., Boirie, Y., Wallberg-Henriksson, H., et al. (2005) · Diabetes · doi:10.2337/diabetes.54.9.2685 · Cited by 369 · cited 2×
“Mfn2 expression is downregulated in skeletal muscle in animal or human obesity and in type 2 diabetic patients (16,20).”
BackgroundSelf-citationPGC-1, a versatile coactivator
Knutti, D., & Kralli, A. (2001) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(01)00457-x · Cited by 294
Boss, O., Samec, S., Kühne, F., Bijlenga, P., Assimacopoulos‐Jeannet, F., Seydoux, J., Giacobino, J., & Muzzin, P. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.1.5 · Cited by 276
The PGC-1-related Protein PERC Is a Selective Coactivator of Estrogen Receptor α
Kressler, D., Schreiber, S., Knutti, D., & Kralli, A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201134200 · Cited by 248
Willy, P. J., Murray, I., Qian, J., Busch, B. B., Stevens, W. C., Martin, R., Mohan, R., Zhou, S., Ordentlich, P., Wei, P. Y., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401420101 · Cited by 200
Laganière, J., Tremblay, G. B., Dufour, C. R., Giroux, S., Rousseau, F., & Giguère, V. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313543200 · Cited by 162
Activation of cardiac Cdk9 represses PGC‐1 and confers a predisposition to heart failure
Sano, M., Wang, S. C., Shirai, M., Scaglia, F., Xie, M., Sakai, S., Tanaka, T., Kulkarni, P. A., Barger, P. M., Youker, K. A., et al. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600351 · Cited by 156
Suppression of β Cell Energy Metabolism and Insulin Release by PGC-1α
Yoon, J. C., Xu, G., Deeney, J. T., Yang, S.-N., Rhee, J., Puigserver, P., Levens, A. R., Yang, R., Zhang, C.-Y., Lowell, B. B., et al. (2003) · Developmental Cell · doi:10.1016/s1534-5807(03)00170-9 · Cited by 143
Boss, O., Bachman, E. S., Vidal‐Puig, A., Zhang, C., Peroni, O. D., & Lowell, B. B. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.1145 · Cited by 100
Orphan Nuclear Receptor Nur77 Is Involved in Caspase-independent Macrophage Cell Death
Kim, S. O., Ono, K., Tobias, P. S., & Han, J. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021842 · Cited by 87
Santalucı́a, T., Moreno, H., Palacı́n, M., Yacoub, M. H., Brand, N. J., & Zorzano, A. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.5091 · Cited by 83
Self-citationMingrone, G., Manco, M., Calvani, M., Castagneto, M., Naon, D., & Zorzano, A. (2005) · Diabetologia · doi:10.1007/s00125-005-1918-9 · Cited by 68
Self-citationMoreno, H., Serrano, A. L., Santalucı́a, T., Gumà, A., Cantó, C., Brand, N. J., Palacı́n, M., Schiaffino, S., & Zorzano, A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306609200 · Cited by 54
Self-citationGómez‐Ambrosi, J., Frühbeck, G., & Martínez, J. A. (2001) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(01)00451-8 · Cited by 43
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Metadata
- Authors
- Soriano, F. X., Liesa, M., Bach, D., Chan, D. C., Palacín, M., & Zorzano, A.
- Affiliations
- Institute for Research in Biomedicine (ES)
- California Institute of Technology (US)
- Institute for Research in Biomedicine (IRB), Scientific Park of Barcelona, and Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2006-06-01
- Volume
- 55
- Issue
- 6
- Pages
- 1783-1791
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2109879006
- Semantic Scholar
- 17041cc2388633b2d920ee981de5eb2d025199be
- Cited by
- 343
- References
- 39
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 13 · 2023: 12 · 2022: 20 · 2021: 13 · 2020: 24 · 2019: 18 · 2018: 25 · 2017: 20 · 2016: 24 · 2015: 19 · 2014: 19 · 2013: 21 · 2012: 27
- FWCI
- 7.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- Johns Hopkins University
- Generalitat de Catalunya
- Instituto Danone
- Instituto de Salud Carlos III
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- 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
- Keywords
- mitofusin 2, PGC-1α, estrogen-related receptor alpha, mitochondrial fusion, mitochondrial metabolism, energy expenditure, cold exposure, beta3-adrenergic agonists, skeletal muscle, brown adipose tissue, transcriptional regulation, mitochondrial membrane potential, insulin resistance, type 2 diabetes
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Adipose Tissue, Brown, Cells, Cultured, Cold Temperature, Dioxoles, Heat-Shock Proteins, HeLa Cells, Humans, Male, Membrane Proteins, Mitochondria, Muscle, Protein Binding, RNA, Messenger, Transcription Factors, Transfection, Blotting, Western, Signal Transduction, Gene Expression, Rats, Wistar, Muscle, Skeletal, GTP Phosphohydrolases, Mitochondrial Proteins, Electrophoretic Mobility Shift Assay, Chromatin Immunoprecipitation, Estrogen Receptor alpha, Mice, Rats
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