ArticleNature communications2022
Mitofusin 1 and 2 regulation of mitochondrial DNA content is a critical determinant of glucose homeostasis.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 87 citations in OpenAlex.
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- The central role of mitochondrial dysfunction in neurodegeneration: implications for therapy.Molecular and cellular biochemistry · 2026Review
- Review
- Toxicity Evaluation of Nano-Sized Particles by Analysis of mtDNA Content and Expression Levels of Genes Required for mtDNA Maintenance: A Meta-Analysis of Pre-Clinical Studies.Antioxidants (Basel, Switzerland) · 2026Review
- Disease-causing MFN2 mutants impair mitochondrial fission dynamics by distinct DRP1 dysregulation.Cell death & disease · 2026Article
- Role of mitochondrial translation in modulating inflammatory disease outcome: Current knowledge and future perspectives.The Journal of biological chemistry · 2026Review
- Targeting the Gut-Liver Mitochondria Axis in MASLD: Mechanisms and Therapeutic Perspectives.Current medical science · 2026Review
- Mitochondria as Epigenetic Regulators of β-Cell Identity and Plasticity: A Metabolo-Epigenetic Perspective.Cells · 2026Review
- Dimeric PKM2 in chondrocytes impairs mitochondrial homeostasis in osteoarthritis.Cell death & disease · 2026Article
- Review
- Mitochondria-associated programmed cell death in pancreatic β cell of T2DM.Apoptosis : an international journal on programmed cell death · 2026Review
- Dietary chromium picolinate-promoted oxidative phosphorylation may be a potential mean to improve hypoxia tolerance of juvenile grass carp (Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- Mitochondrial development and remodeling occur at pancreatic progenitor stage during induction of stem cell-derived islet organoids.Frontiers in endocrinology · 2026Article
- Mitochondria-mediated inflammation and diabetic wound healing: mechanisms and therapeutic strategies.Frontiers in pharmacology · 2026Review
- Novel therapeutic strategies targeting mitochondrial quality control for metabolic dysfunction-associated steatotic liver disease.Frontiers in physiology · 2026Review
- Mitochondrial transfer-mediated metabolic reprogramming and drug resistance in bone metastasis: mechanisms and therapeutic strategies.Frontiers in immunology · 2026Review
- Dietary Geranylgeraniol Mitigates Pain-Associated Behaviors via Improving Mitochondrial Function and Colon Integrity and Suppressing Neuroinflammation in Male Diabetic Neuropathy Rats.International journal of molecular sciences · 2025Article
- Limitations in PPARα-dependent mitochondrial programming restrain the differentiation of human stem cell-derived β cells.Nature communications · 2025Article
- Mitochondria in focus: From structure and function to their role in human diseases. A review.Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia · 2025Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The dynamin-like GTPases Mitofusin 1 and 2 (Mfn1 and Mfn2) are essential for mitochondrial function, which has been principally attributed to their regulation of fission/fusion dynamics. Here, we report that Mfn1 and 2 are critical for glucose-stimulated insulin secretion (GSIS) primarily through control of mitochondrial DNA (mtDNA) content. Whereas Mfn1 and Mfn2 individually were dispensable for glucose homeostasis, combined Mfn1/2 deletion in β-cells reduced mtDNA content, impaired mitochondrial morphology and networking, and decreased respiratory function, ultimately resulting in severe glucose intolerance. Importantly, gene dosage studies unexpectedly revealed that Mfn1/2 control of glucose homeostasis was dependent on maintenance of mtDNA content, rather than mitochondrial structure. Mfn1/2 maintain mtDNA content by regulating the expression of the crucial mitochondrial transcription factor Tfam, as Tfam overexpression ameliorated the reduction in mtDNA content and GSIS in Mfn1/2-deficient β-cells. Thus, the primary physiologic role of Mfn1 and 2 in β-cells is coupled to the preservation of mtDNA content rather than mitochondrial architecture, and Mfn1 and 2 may be promising targets to overcome mitochondrial dysfunction and restore glucose control in diabetes.
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Registered trials
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