ArticleNature chemical biology2023
Small molecule agonist of mitochondrial fusion repairs mitochondrial dysfunction.
Article in Nature chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 69 citations in OpenAlex.
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- Mitochondrial dysfunction‑driven ferroptosis in cerebral ischemia‑reperfusion injury: Mechanisms and therapeutic strategies (Review).Molecular medicine reports · 2026Review
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- Targeting Mitochondria in Aging-Related Diseases: Therapeutic Potential and Obstacles.MedComm · 2026Review
- A plant vesicle-dendritic cell chimera for enhancing cancer immunotherapy.Nature communications · 2026Article
- Restoring mitochondrial health after blast-induced traumatic brain injury: modifiable factors and therapeutic opportunities.npj metabolic health and disease · 2026Review
- Dynamic collaboration between mitochondria and organelles: mechanisms, functions, and disease implications.Apoptosis : an international journal on programmed cell death · 2026Review
- Mitochondria in T‑cell tumor immunity and tumor therapies targeting mitochondria (Review).Oncology reports · 2026Review
- Mechanistic insights and therapeutic interventions of mitochondrial quality control in chemotherapy-related cognitive impairment.Neoplasia (New York, N.Y.) · 2026Review
- Endoplasmic Reticulum-Mitochondrial Crosstalk in Calcium Regulation: Mechanistic Insights and Therapeutic Implications in Traumatic Brain Injury.Molecular neurobiology · 2026Review
- The mitochondrial translocation of phosphorylated EZH2 promotes PARP inhibitor resistance in BRCA1-deficient epithelial ovarian cancer.Cell discovery · 2026Article
- Role of mitochondrial dysfunction in muscle wasting in cancer cachexia: a narrative review.Journal of translational medicine · 2026Review
- Novel small molecule derivatives improve survivability in the cellular model of Huntington's diseaseRSC medicinal chemistry · 2026Article
- Ferroptosis in cancer toward molecular insights and clinical translation in pancreatic cancer.Molecular cancer · 2026Review
- Regulation of apoptosis, ferroptosis, and pyroptosis mediated by acetylation.Cell death discovery · 2026Review
- Mitochondrial programmed cell death in bronchopulmonary dysplasia: mechanisms and therapeutic targets.Frontiers in physiology · 2026Review
- Mitochondrial fission and fusion in inflammatory diseases: mechanisms and therapeutic implications.Journal of translational medicine · 2025Review
- Article
- A Small-Molecule Mitofusin 1 Agonist Enhances Islet Survival Under Hypoxic Conditions In Vitro and Improves Transplantation Outcomes.Biomolecules · 2025Article
- Prolonged sepsis triggers abnormal mitochondrial dynamics in the limb muscles and diaphragm.Molecular and cellular biochemistry · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
29 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Membrane dynamics are important to the integrity and function of mitochondria. Defective mitochondrial fusion underlies the pathogenesis of multiple diseases. The ability to target fusion highlights the potential to fight life-threatening conditions. Here we report a small molecule agonist, S89, that specifically promotes mitochondrial fusion by targeting endogenous MFN1. S89 interacts directly with a loop region in the helix bundle 2 domain of MFN1 to stimulate GTP hydrolysis and vesicle fusion. GTP loading or competition by S89 dislodges the loop from the GTPase domain and unlocks the molecule. S89 restores mitochondrial and cellular defects caused by mitochondrial DNA mutations, oxidative stress inducer paraquat, ferroptosis inducer RSL3 or CMT2A-causing mutations by boosting endogenous MFN1. Strikingly, S89 effectively eliminates ischemia/reperfusion (I/R)-induced mitochondrial damage and protects mouse heart from I/R injury. These results reveal the priming mechanism for MFNs and provide a therapeutic strategy for mitochondrial diseases when additional mitochondrial fusion is beneficial.
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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.