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.
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“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
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“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
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Mitofusin 2 tethers endoplasmic reticulum to mitochondria
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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
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