ArticleNature2016
Correcting mitochondrial fusion by manipulating mitofusin conformations.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers.
What it found
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Who cites it
153 citing papers in PubMed, 237 citations in OpenAlex.
- Mitofusin Activation Delays Aging inCells · 2026Article
- Neuromuscular Dysfunction and Charcot-Marie-Tooth Disease Reversal in Mfn2 T105M Knock-In Rats.International journal of molecular sciences · 2026Article
- Disease-causing MFN2 mutants impair mitochondrial fission dynamics by distinct DRP1 dysregulation.Cell death & disease · 2026Article
- The SDF-1α/CXCR4 axis regulates chondrocyte mitochondrial dynamics via the ERK/AMPKα pathway.Cell communication and signaling : CCS · 2026Article
- Using image classifiers to predict CMT2A disease-relevant mitochondrial motility phenotypes in iPSC motor neurons.bioRxiv : the preprint server for biology · 2026Article
- AAVrh74.tMCK.NT-3 Surrogate Gene Therapy in a Mouse Model of CMT2A.International journal of molecular sciences · 2026Article
- Mutant CHCHD10 disrupts cytochrome c oxidation and activates mitochondrial retrograde signaling.EMBO molecular medicine · 2026Article
- Hereditary Polyneuropathies in the Era of Precision Medicine: Genetic Complexity and Emerging Strategies.Genes · 2026Review
- Advances and challenges in modeling Charcot-Marie-Tooth type 2A using iPSC-derived models.Stem cell reports · 2025Review
- Mitochondrial targets in ischaemic heart disease and heart failure, and their potential for a more efficient clinical translation. A scientific statement of the ESC Working Group on Cellular Biology of the Heart and the ESC Working Group on Myocardial Function.European journal of heart failure · 2025Review
- Ultrastructure analysis of mitochondria, lipid droplet and sarcoplasmic reticulum apposition in human heart failure.Journal of molecular and cellular cardiology plus · 2025Article
- The complex web of membrane contact sites in brain aging and neurodegeneration.Cellular and molecular life sciences : CMLS · 2025Review
- Modulating mitochondrial dynamics in CMT2A: a multifaceted platform for drug discovery and evaluation.Biophysics reports · 2025Article
- Endosomal RFFL ubiquitin ligase regulates mitochondrial morphology by targeting mitofusin 2.Journal of cell science · 2025Article
- Mitochondrial quality control as a therapeutic target in cardiovascular disease: Mechanistic insights and future directions.Journal of translational internal medicine · 2025Article
- OPA1 mutations in dominant optic atrophy: domain-specific defects in mitochondrial fusion and apoptotic regulation.Journal of translational medicine · 2025Article
- High urea promotes mitochondrial fission and functional impairments in astrocytes inducing anxiety-like behavior in chronic kidney disease mice.Metabolic brain disease · 2025Article
- Mitochondrial Dysfunction in Cardiovascular Diseases.International journal of molecular sciences · 2025Review
- Molecular mechanisms of mitochondrial dynamics.Nature reviews. Molecular cell biology · 2025Review
- Role of mitochondrial quality control in neurodegenerative disease progression.Frontiers in cellular neuroscience · 2025Review
93 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
Mitochondria are dynamic organelles that exchange contents and undergo remodelling during cyclic fusion and fission. Genetic mutations in MFN2 (the gene encoding mitofusin 2) interrupt mitochondrial fusion and cause the untreatable neurodegenerative condition Charcot-Marie-Tooth disease type 2A (CMT2A). It has not yet been possible to directly modulate mitochondrial fusion, in part because the structural basis of mitofusin function is not completely understood. Here we show that mitofusins adopt either a fusion-constrained or a fusion-permissive molecular conformation, directed by specific intramolecular binding interactions, and demonstrate that mitofusin-dependent mitochondrial fusion can be regulated in mouse cells by targeting these conformational transitions. On the basis of this model, we engineered a cell-permeant minipeptide to destabilize the fusion-constrained conformation of mitofusin and promote the fusion-permissive conformation, reversing mitochondrial abnormalities in cultured fibroblasts and neurons that harbour CMT2A-associated genetic defects. The relationship between the conformational plasticity of mitofusin 2 and mitochondrial dynamism reveals a central mechanism that regulates mitochondrial fusion, the manipulation of which can correct mitochondrial pathology triggered by defective or imbalanced mitochondrial dynamics.
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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.