ArticleNature communications2020
Pharmacological targeting of MCL-1 promotes mitophagy and improves disease pathologies in an Alzheimer's disease mouse model.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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Who cites it
109 citing papers in PubMed, 185 citations in OpenAlex.
- Mitochondrial quality control in acute liver injury and its therapeutic implications (Review).Molecular medicine reports · 2026Review
- Autophagy and selective autophagy receptors: Key players against Alzheimer's disease.Neural regeneration research · 2026Article
- Mitophagy in Metabolic Dysfunction-Associated Fatty Liver Disease: Mechanisms, Regulatory Networks, and Therapeutic Perspectives.Inflammation · 2026Review
- Acylglycerol Kinase Inhibition Restores Mitophagy and Alleviates Alzheimer's Disease Pathology.MedComm · 2026Article
- Reprogramming Neuroinflammation: Mitochondrial Targets and Immune Checkpoint Inhibitors in Alzheimer's Disease.Molecular neurobiology · 2026Review
- Review
- Mitochondrial homeostasis: the central hub governing the progression of atherosclerosis.Precision clinical medicine · 2026Review
- Aging Impairs Macrophage Phagocytosis Through Mitochondrial ROS-Induced Collagen Production.Aging cell · 2026Article
- Mitochondrial dynamics in neurodevelopment and neurodevelopmental disorders.Nature reviews. Neuroscience · 2026Review
- Phosphorylated ubiquitin is a secondary messenger and an epigenetic mark mediating mitochondria to nucleus signaling.bioRxiv : the preprint server for biology · 2026Article
- Allyl-substituted ALT001 promotes alternative mitophagy and improves therapeutic outcomes in Alzheimer's disease models.Scientific reports · 2026Article
- Structure-Activity Relationship Studies Enable Optimization of a Small-Molecule Autophagy Activator and Evaluation of Effects on Cell Death Pathways.ACS pharmacology & translational science · 2026Article
- Recovery from apoptosis in photoreceptor cells: A role for mitophagy.Cell death & disease · 2026Article
- Mitophagy in the pathogenesis and management of disease.Cell research · 2026Review
- Targeting MCL1 by UMI-77 to induce mitophagy alleviates renal tubular epithelial cells injury in acute kidney injury.Scientific reports · 2025Article
- Hv1 inhibition rescues AD pathology by restoring microglial mitochondrial function and enhancing mitochondrial transfer.Experimental & molecular medicine · 2025Article
- MCL1 modulates mTORC1 signaling to promote bioenergetics and tumorigenesis.Nature communications · 2025Article
- Inhibition of MCL-1 to eliminate senescent cells and mitigate renal fibrosis in aristolochic acid nephropathy.Cell death & disease · 2025Article
- Rac1 promotes proximal tubule kidney repair by coupling the actin cytoskeleton to mitochondrial function.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
49 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is increasing evidence that inducing neuronal mitophagy can be used as a therapeutic intervention for Alzheimer's disease. Here, we screen a library of 2024 FDA-approved drugs or drug candidates, revealing UMI-77 as an unexpected mitophagy activator. UMI-77 is an established BH3-mimetic for MCL-1 and was developed to induce apoptosis in cancer cells. We found that at sub-lethal doses, UMI-77 potently induces mitophagy, independent of apoptosis. Our mechanistic studies discovered that MCL-1 is a mitophagy receptor and directly binds to LC3A. Finally, we found that UMI-77 can induce mitophagy in vivo and that it effectively reverses molecular and behavioral phenotypes in the APP/PS1 mouse model of Alzheimer's disease. Our findings shed light on the mechanisms of mitophagy, reveal that MCL-1 is a mitophagy receptor that can be targeted to induce mitophagy, and identify MCL-1 as a drug target for therapeutic intervention in Alzheimer's disease.
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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.