The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Mitofusin 2 in POMC Neurons Connects ER Stress with Leptin Resistance and Energy Imbalance
Open accessAbstract
Mitofusin 2 (MFN2) plays critical roles in both mitochondrial fusion and the establishment of mitochondria-endoplasmic reticulum (ER) interactions. Hypothalamic ER stress has emerged as a causative factor for the development of leptin resistance, but the underlying mechanisms are largely unknown. Here, we show that mitochondria-ER contacts in anorexigenic pro-opiomelanocortin (POMC) neurons in the hypothalamus are decreased in diet-induced obesity. POMC-specific ablation of Mfn2 resulted in loss of mitochondria-ER contacts, defective POMC processing, ER stress-induced leptin resistance, hyperphagia, reduced energy expenditure, and obesity. Pharmacological relieve of hypothalamic ER stress reversed these metabolic alterations. Our data establish MFN2 in POMC neurons as an essential regulator of systemic energy balance by fine-tuning the mitochondrial-ER axis homeostasis and function. This previously unrecognized role for MFN2 argues for a crucial involvement in mediating ER stress-induced leptin resistance.
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
“However, the depletion of Mfn2 in the anorexigenic POMC neurons causes severe obesity and leptin resistance probably by affecting ER-stress (Schneeberger et al., 2013).”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Schneeberger et al., 2013
In the citing paper
“the depletion of Mfn2 in the anorexigenic POMC neurons causes severe obesity and leptin resistance probably by affecting ER-stress (Schneeberger et al., 2013).”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Schneeberger et al., 2013
In the citing paper
“Defective mitochondrial dynamics and mitochondrial-ER communication in hypothalamic POMC and AgRP neurons might actually modify feeding behavior and whole-body energy homeostasis (Dietrich et al, 2013; Schneeberger et al, 2013).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Schneeberger et al, 2013
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
Mitochondrial Fission, Fusion, and Stress
Youle, R. J., & van der Bliek, A. M. (2012) · Science · doi:10.1126/science.1219855 · Cited by 3,674
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
Mitofusin 2 tethers endoplasmic reticulum to mitochondria
de Brito, O. M., & Scorrano, L. (2008) · Nature · doi:10.1038/nature07534 · Cited by 2,442
Hypothalamic IKKβ/NF-κB and ER Stress Link Overnutrition to Energy Imbalance and Obesity
Zhang, X., Zhang, G., Zhang, H., Karin, M., Bai, H., & Cai, D. (2008) · Cell · doi:10.1016/j.cell.2008.07.043 · Cited by 1,350
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
Pesta, D. H., & Gnaiger, E. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-382-0_3 · Cited by 1,005
Mitochondrial fusion protects against neurodegeneration in the cerebellum
Chen, H., McCaffery, J. M., & Chan, D. C. (2007) · Cell · doi:10.1016/j.cell.2007.06.026 · Cited by 924
Endoplasmic Reticulum Stress Plays a Central Role in Development of Leptin Resistance
Ozcan, L., Ergin, A. S., Lu, A., Chung, J., Sarkar, S., Nie, D., Myers, M. G., & Ozcan, U. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2008.12.004 · Cited by 875
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
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
Widespread recombinase expression using FLPeR (Flipper) mice
Farley, F. W., Soriano, P. M., Steffen, L. S., & Dymecki, S. M. (2000) · genesis · doi:10.1002/1526-968x(200011/12)28:3/4 · Cited by 602
AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons
Claret, M., Smith, M. A., Batterham, R. L., Selman, C., Choudhury, A. I., Fryer, L. G. D., Clements, M., Al‐Qassab, H., Heffron, H., Xu, A. W., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31516 · Cited by 522
Forkhead protein FoxO1 mediates Agrp-dependent effects of leptin on food intake
Kitamura, T., Feng, Y., Kitamura, Y., Chua, S. C., Xu, A. W., Barsh, G. S., Rossetti, L., & Accili, D. (2006) · Nature Medicine · doi:10.1038/nm1392 · Cited by 458
From neuroanatomy to behavior: central integration of peripheral signals regulating feeding behavior
Williams, K. W., & Elmquist, J. K. (2012) · Nature Neuroscience · doi:10.1038/nn.3217 · Cited by 435
PI3K integrates the action of insulin and leptin on hypothalamic neurons
Xu, A. W. (2005) · Journal of Clinical Investigation · doi:10.1172/jci200524301 · Cited by 420
Central nervous system control of metabolism
Myers, M. G., & Olson, D. P. (2012) · Nature · doi:10.1038/nature11705 · Cited by 399
Papanicolaou, K. N., Khairallah, R. J., Ngoh, G. A., Chikando, A. C., Luptak, I., O’Shea, K. M., Riley, D. D., Lugus, J. J., Colucci, W. S., Lederer, W. J., et al. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.00911-10 · Cited by 371
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
Münzberg, H., Huo, L., Nillni, E. A., Hollenberg, A. N., & Bjørbæk, C. (2003) · Endocrinology · doi:10.1210/en.2002-221037 · Cited by 328
Dietrich, M. O., Liu, Z.-W., & Horvath, T. L. (2013) · Cell · doi:10.1016/j.cell.2013.09.004 · Cited by 306
Self-citationDiano, S., Liu, Z.-W., Jeong, J. K., Dietrich, M. O., Ruan, H., Kim, E., Suyama, S., Kelly, K., Gyengési, E., Arbiser, J. L., et al. (2011) · Nature Medicine · doi:10.1038/nm.2421 · Cited by 284
Papanicolaou, K. N., Ngoh, G. A., Dabkowski, E. R., O’Connell, K. A., Júnior, R. F. R., Stanley, W. C., & Walsh, K. X. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00833.2011 · Cited by 208
Endoplasmic Reticulum Stress Induces Leptin Resistance
Hosoi, T., Sasaki, M., Miyahara, T., Hashimoto, C., Matsuo, S., Yoshii, M., & Ozawa, K. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.050070 · Cited by 206
Mitochondrial fusion proteins: Dual regulators of morphology and metabolism
Antonio Zorzano, A., Liesa, M., Sebastián, D., Segalés, J., & Palacín, M. (2010) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2010.01.002 · Cited by 204
Mitofusin2 Mutations Disrupt Axonal Mitochondrial Positioning and Promote Axon Degeneration
Misko, A. L., Sasaki, Y., Tuck, E. J., Milbrandt, J., & Baloh, R. H. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.6338-11.2012 · Cited by 200
Garcia-Roves, P. M., Osler, M. E., Holmström, M. H., & Zierath, J. R. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805078200 · Cited by 190
Hernández-Alvarez, M. I., Thabit, H., Burns, N., Shah, S., Brema, I., Hatunic, M., Finucane, F., Liesa, M., Chiellini, C., Naon, D., et al. (2010) · Diabetes Care · doi:10.2337/dc09-1305 · Cited by 189
Self-citationLoss of Mitofusin 2 Promotes Endoplasmic Reticulum Stress
Ngoh, G. A., Papanicolaou, K. N., & Walsh, K. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.359174 · Cited by 183
Mitofusin 2 is necessary for striatal axonal projections of midbrain dopamine neurons
Lee, S., Sterky, F. H., Mourier, A., Terzioglu, M., Cullheim, S., Olson, L., & Larsson, N. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds352 · Cited by 180
Pham, A. H., Meng, S., Chu, Q. N., & Chan, D. C. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds311 · Cited by 170
Al‐Qassab, H., Smith, M. A., Irvine, E. E., Guillermet‐Guibert, J., Claret, M., Choudhury, A. I., Selman, C., Piipari, K., Clements, M., Lingard, S. J., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.09.008 · Cited by 165
Won, J. C., Jang, P., Namkoong, C., Koh, E. H., Kim, S. K., Park, J., Lee, K., & Kim, M. (2009) · Obesity · doi:10.1038/oby.2009.194 · Cited by 153
Hypothalamic proopiomelanocortin processing and the regulation of energy balance
Wardlaw, S. L. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.10.107 · Cited by 153
Holmström, M. H., Iglesias-Gutierrez, E., Zierath, J. R., & Garcia-Roves, P. M. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00159.2011 · Cited by 137
Prolylcarboxypeptidase regulates food intake by inactivating α-MSH in rodents
Wallingford, N. M., Perroud, B., Gao, Q., Coppola, A. M., Gyengési, E., Liu, Z.-W., Gao, X., Diament, A. L., Haus, K. A., Shariat‐Madar, Z., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37209 · Cited by 133
Endoplasmic reticulum: nutrient sensor in physiology and pathology
Mandl, J., Mészáros, T., Bánhegyi, G., Hunyady, L., & Csala, M. (2009) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2009.01.003 · Cited by 115
Hypothalamic Control of Lipid Metabolism: Focus on Leptin, Ghrelin and Melanocortins
Diéguez, C., Vazquez, M. J., Romero, A., López, M., & Nogueiras, R. (2011) · Neuroendocrinology · doi:10.1159/000328122 · Cited by 109
Gamber, K. M., Huo, L., Ha, S., Hairston, J. E., Greeley, S., & Bjørbæk, C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030485 · Cited by 96
Central Leptin Receptor Action and Resistance in Obesity
Bjørbæk, C. (2009) · Journal of Investigative Medicine · doi:10.2310/jim.0b013e3181bb0d49 · Cited by 88
Mice lacking δ‐opioid receptors resist the development of diet‐induced obesity
Czyzyk, T. A., Romero, A., Pintar, J. E., McKinzie, J. H., Tschöp, M. H., Statnick, M. A., & Nogueiras, R. (2012) · The FASEB Journal · doi:10.1096/fj.12-208041 · Cited by 73
Hypothalamic mitochondrial dysfunction associated with anorexia in the anx/anx mouse
Lindfors, C., Nilsson, I. A. K., García-Rovés, P. M., Zuberi, A. R., Karimi, M., Donahue, L. R., Roopenian, D. C., Mulder, J., Uhlén, M., Ekström, T. J., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1114863108 · Cited by 61
Gyengési, E., Paxinos, G., & Andrews, Z. B. (2012) · Current Neuropharmacology · doi:10.2174/157015912804143496 · Cited by 61
Deletion of Lkb1 in Pro-Opiomelanocortin Neurons Impairs Peripheral Glucose Homeostasis in Mice
Claret, M., Smith, M. A., Knauf, C., Al‐Qassab, H., Woods, A., Heslegrave, A., Piipari, K., Emmanuel, J. J., Colom, A., Valet, P., et al. (2011) · Diabetes · doi:10.2337/db10-1055 · Cited by 52
Gyengési, E., Paxinos, G., & Andrews, Z. B. (2012) · Current Neuropharmacology · doi:10.2174/157015912804499438 · Cited by 46
Hypothalamic control of energy and glucose metabolism
Sisley, S. R., & Sandoval, D. A. (2011) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-011-9189-x · Cited by 45
Mitochondria in response to nutrients and nutrient-sensitive pathways
Baltzer, C., Tiefenböck, S. K., & Frei, C. (2010) · Mitochondrion · doi:10.1016/j.mito.2010.07.009 · Cited by 28
Hernández‐Álvarez, M. I., Chiellini, C., Manco, M., Naón, D., Liesa, M., Palacı́n, M., Mingrone, G., & Zorzano, A. (2009) · Diabetologia · doi:10.1007/s00125-009-1403-y · Cited by 27
Flagged first, then by citations
Cited by
Sorted by citations
The cell biology of mitochondrial membrane dynamics
Giacomello, M., Pyakurel, A., Glytsou, C., & Scorrano, L. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0210-7 · Cited by 1,550
Mitochondrial ROS Signaling in Organismal Homeostasis
Shadel, G. S., & Horvath, T. L. (2015) · Cell · doi:10.1016/j.cell.2015.10.001 · Cited by 1,353
Mitochondrial Dynamics and Metabolic Regulation
Wai, T., & Langer, T. (2016) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2015.12.001 · Cited by 1,354
The machineries, regulation and cellular functions of mitochondrial calcium
Giorgi, C., Marchi, S., & Pinton, P. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0052-8 · Cited by 941
Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity
Timper, K., & Brüning, J. C. (2017) · Disease Models & Mechanisms · doi:10.1242/dmm.026609 · Cited by 851
Metadata
- Authors
- Schneeberger, M., Dietrich, M. O., Sebastián, D., Imbernón, M., Castaño, C., Garcia, A., Esteban, Y., Gonzalez-Franquesa, A., Rodríguez, I. C., Bortolozzi, A., Garcia-Roves, P. M., Gomis, R., Nogueiras, R., Horvath, T. L., Zorzano, A., & Claret, M.
- Affiliations
- Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (ES)
- Universidade Federal do Rio Grande do Sul (BR)
- Universidade de Santiago de Compostela (ES)
- Corresponding author
- Claret, Marc
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 155
- Issue
- 1
- Pages
- 172-187
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3839088
- OpenAlex
- W1972621040
- Cited by
- 519
- References
- 47
- Citations by year
- 2026: 18 · 2025: 22 · 2024: 28 · 2023: 31 · 2022: 32 · 2021: 41 · 2020: 52 · 2019: 53 · 2018: 52 · 2017: 72 · 2016: 48 · 2015: 28 · 2014: 36 · 2013: 4
- FWCI
- 20.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- RUNA. Repositorio Institucional del Sergas (Servicio Gallego de Salud (SERGAS)) (submittedVersion, other-oa)
- Funders
- National Institutes of Health (DP1OD006850)
- National Institute on Aging (R01AG040236)
- National Institute of Diabetes and Digestive and Kidney Diseases (DP1DK098058, DP1 DK006850)
- National Institute of Neurological Disorders and Stroke (P01NS062686)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- mitofusin 2, proopiomelanocortin neurons, hypothalamus, endoplasmic reticulum stress, leptin resistance, diet-induced obesity, mitochondrial fusion, energy balance, hyperphagia, energy expenditure, POMC processing
- MeSH terms
- Animals, Hypothalamus, Mice, Inbred C57BL, Neurons, Obesity, Pro-Opiomelanocortin, GTP Phosphohydrolases, Leptin, Mice, Endoplasmic Reticulum Stress
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
