ArticleNature2017
MFN1 structures reveal nucleotide-triggered dimerization critical for mitochondrial fusion.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 194 papers, 1 of them a synthesis that pooled it.
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Who cites it
194 citing papers in PubMed, 1 synthesis or guideline pooled it, 317 citations in OpenAlex.
- The molecular mechanisms of mitochondrial dynamics and mitophagy and their complex association with cancer drug resistance.Journal of translational medicine · 2025Pooled it
- Mitochondrial Dysfunction: A Critical Link Between Maternal Diet and Offspring Metabolic Health.Biomolecules · 2026Review
- Higher-order structural organization of mitochondrial metabolism.The Journal of biological chemistry · 2026Review
- Renaissance of Traditional Mineral Drugs in Cancer: Advanced Delivery Strategies and Bioengineering Approaches.Pharmaceutics · 2026Review
- Disease-causing MFN2 mutants impair mitochondrial fission dynamics by distinct DRP1 dysregulation.Cell death & disease · 2026Article
- Nitrite increases mitofusin-1 levels to inhibit vascular smooth muscle cell proliferation and prevent intimal hyperplasia.Redox biology · 2026Article
- Regulation of mitochondrial function during spermatogenesis and sperm maturation.Cellular & molecular biology letters · 2026Review
- A robust workflow for 3D imaging of human mitochondria using cryo-electron tomography.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial dynamics and cancer: mechanisms and targeted therapy.Cell biology and toxicology · 2026Review
- Homoisoflavanone Delays Colorectal Cancer Progression via DNA Damage-Induced Mitochondrial Apoptosis and Parthanatos-Like Cell Death.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mitochondrial Homeostasis in Diabetic Cardiomyopathy: From Dysfunction to Therapeutic Strategies.Antioxidants (Basel, Switzerland) · 2026Review
- Extracellular matrix signals promote actin-dependent mitochondrial elongation and activity.iScience · 2026Article
- Neuronal mitochondrial dynamics: roles in brain disorders and therapeutic potential.Acta pharmacologica Sinica · 2026Article
- Pathogenic roles of the IMNEPD-associated PTRH2 mutants in aggravating mitochondrial dynamics and its rescue.Molecular medicine (Cambridge, Mass.) · 2026Article
- MIRO1-mediated mitochondrial fusion is required for stomatal immunity in Arabidopsis.Nature plants · 2026Article
- Organelle-specific regulation of ferroptosis.Biology direct · 2026Review
- Arsenic trioxide-induced acute kidney injury: OPA1- and Drp1-mediated mitochondrial dynamics imbalance, PINK1/Parkin-dependent mitophagy, and Chuanhuang Fang III.Frontiers in molecular biosciences · 2026Article
- Metabolic-epigenetic axis in cardiovascular inflammatory injury: regulatory mechanisms and intervention strategies.Frontiers in cardiovascular medicine · 2026Review
- Mitochondrial fission and fusion in inflammatory diseases: mechanisms and therapeutic implications.Journal of translational medicine · 2025Review
- MYC affects mitochondrial function in IgA nephropathy by promoting the degradation of MFN1 through HRD1.Immunologic research · 2025Article
134 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Mitochondria are double-membraned organelles with variable shapes influenced by metabolic conditions, developmental stage, and environmental stimuli. Their dynamic morphology is a result of regulated and balanced fusion and fission processes. Fusion is crucial for the health and physiological functions of mitochondria, including complementation of damaged mitochondrial DNAs and the maintenance of membrane potential. Mitofusins are dynamin-related GTPases that are essential for mitochondrial fusion. They are embedded in the mitochondrial outer membrane and thought to fuse adjacent mitochondria via combined oligomerization and GTP hydrolysis. However, the molecular mechanisms of this process remain unknown. Here we present crystal structures of engineered human MFN1 containing the GTPase domain and a helical domain during different stages of GTP hydrolysis. The helical domain is composed of elements from widely dispersed sequence regions of MFN1 and resembles the 'neck' of the bacterial dynamin-like protein. The structures reveal unique features of its catalytic machinery and explain how GTP binding induces conformational changes to promote GTPase domain dimerization in the transition state. Disruption of GTPase domain dimerization abolishes the fusogenic activity of MFN1. Moreover, a conserved aspartate residue trigger was found to affect mitochondrial elongation in MFN1, probably through a GTP-loading-dependent domain rearrangement. Thus, we propose a mechanistic model for MFN1-mediated mitochondrial tethering, and our results shed light on the molecular basis of mitochondrial fusion and mitofusin-related human neuromuscular disorders.
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