ArticleCell2013
Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance.
Article in Cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 290 papers.
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Who cites it
290 citing papers in PubMed, 505 citations in OpenAlex.
- Tert-Butylhydroquinone Reversed Age-Dependent Hypothalamic Mitochondrial Dysfunction Linking Maternal Fructose Exposure to Synaptic Vulnerability.Molecular neurobiology · 2026Article
- POMC AMPKα1 deletion drives male-specific BAT thermogenesis and obesity resistance.EMBO reports · 2026Article
- Mitochondrial quality control in health and disease: mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Mitochondrial Dysfunction: A Critical Link Between Maternal Diet and Offspring Metabolic Health.Biomolecules · 2026Review
- Redefining the timeline: a three-phase framework of hypothalamic microinflammation in metabolic disease.Reviews in endocrine & metabolic disorders · 2026Review
- Glycogen drives the sensory activation of POMC neurons.Nature metabolism · 2026Article
- Hypothalamic regulation of energy homeostasis: Quo vadis.Reviews in endocrine & metabolic disorders · 2026Review
- Hypothalamic endoplasmic reticulum stress drives pubertal precocity due to early-onset obesity in female rodents.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mitofusins are required for specialized mitochondrial morphology and function of rod photoreceptor cells.Frontiers in cell and developmental biology · 2026Article
- Nutri-epigenetics of mitochondrial function and energy homeostasis in obesity.Genes & nutrition · 2025Review
- Insulin evokes release of endozepines from astrocytes of the NTS to modulate glucose metabolism in male rats.Molecular metabolism · 2025Article
- Neurobiology of mitochondrial dynamics in sleep.The Journal of physiology · 2025Review
- Reduced NRF2/Mfn2 activity promotes endoplasmic reticulum stress and senescence in adipose-derived mesenchymal stem cells in hypertrophic obese mice.World journal of stem cells · 2025Article
- Fam163a knockdown and mitochondrial stress in the arcuate nucleus of hypothalamus reduce AgRP neuron activity and differentially regulate mitochondrial dynamics in mice.Acta physiologica (Oxford, England) · 2025Article
- The Role of Mitochondrial AKT1 Signaling in Renal Tubular Injury of Metabolic Syndrome.Kidney international reports · 2025Article
- The structure and function of mitofusin 2 and its role in cardiovascular disease through mediating mitochondria-associated endoplasmic reticulum membranes.Frontiers in cardiovascular medicine · 2025Review
- Modulation of endoplasmic reticulum stress-induced insulin resistance by the low-carbohydrate high-fat ketogenic diet.Frontiers in nutrition · 2025Review
- MFN2-a multifaceted guardian against Parkinson's pathophysiology: mitochondria, ferroptosis, inflammation and oxidative stress.Frontiers in aging neuroscience · 2025Article
- Regulation of BAT thermogenesis via TRPA1-expressing hypothalamic POMC neurons.Animal cells and systems · 2025Article
- Neuroendocrine control of glucose homeostasis: integrative mechanisms from the hypothalamus to the brainstem.Frontiers in endocrinology · 2025Review
230 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 7 institutions in 3 countries.
Funding
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.