ArticleScience advances2025
Putative PINK1/Parkin activators lower the threshold for mitophagy by sensitizing cells to mitochondrial stress.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed.
- Species-dependent activities of the PINK1-parkin axis.Translational neurodegeneration · 2026Review
- Review
- Pharmacological modulation of cGAS-STING-NLRP3 signaling by nano-immunomodulators in Alzheimer and Parkinson disease.Inflammopharmacology · 2026Review
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- Reprogramming Autophagy to Strengthen Antitumour Immunity: Advances in Immunotherapeutic Strategies.Immunology · 2026Review
- Exercise as a Programmable Regulator of Mitophagy Sensitivity in Aging Muscle and Age-Related Disease.IUBMB life · 2026Review
- Targeting of kinases to treat neurodegenerative diseases.Pharmacological reviews · 2026Review
- Mitochondria at the heart of aging: structure, function, and failure.Journal of translational medicine · 2026Review
- Neural cell state modulation bybioRxiv : the preprint server for biology · 2026Article
- Dual regulation of PINK1/PARKIN-mediated mitochondrial autophagy in ovarian cancer progression and drug resistance: mechanisms and therapeutic potentials.Journal of ovarian research · 2026Review
- Sources of Oxidative Stress in Parkinson's Disease: Pathways and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2026Review
- Dietary Polyphenols (Flavonoids) Derived from Plants for Use in Therapeutic Health: Antioxidant Performance, ROS, Molecular Mechanisms, and Bioavailability Limitations.International journal of molecular sciences · 2026Review
- Review
- UQCRC1 deficiency impairs mitophagy via PINK1-dependent mechanisms in Parkinson's disease.NPJ Parkinson's disease · 2026Article
- Physical exercise as a precision strategy for targeted PINK1 recruitment- a mechanistic review.Frontiers in physiology · 2026Review
- Mitochondrial resilience: a convergent framework for pathogenesis and neuroprotection in Parkinson's disease.Frontiers in pharmacology · 2026Review
- The Post-COVID syndrome caused by excessive inflammation: pathogenesis, potential targets and therapeutic agents.Frontiers in pharmacology · 2026Review
- Rethinking PINK1/Parkin-mediated mitophagy in Parkinson's disease: functional continuity and activation-clearance uncoupling.Frontiers in aging neuroscience · 2026Review
- Parkin protects against traumatic brain injury through regulating mitochondrial quality control.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Mitophagy and Cellular Homeostasis in Kidney Diseases: Mechanisms and Potential Therapeutics.International journal of biological sciences · 2026Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
The PINK1/Parkin pathway targets damaged mitochondria for degradation via mitophagy. Genetic evidence implicates impaired mitophagy in Parkinson's disease, making its pharmacological enhancement a promising therapeutic strategy. Here, we characterize two mitophagy activators: a novel Parkin activator, FB231, and the reported PINK1 activator MTK458. Both compounds lower the threshold for mitochondrial toxins to induce PINK1/Parkin-mediated mitophagy. However, global proteomics revealed that FB231 and MTK458 independently induce mild mitochondrial stress, resulting in impaired mitochondrial function and activation of the integrated stress response, effects that result from PINK1/Parkin-independent off-target activities. We find that these compounds impair mitochondria by distinct mechanisms and synergistically decrease mitochondrial function and cell viability in combination with classical mitochondrial toxins. Our findings support a model whereby weak or "silent" mitochondrial toxins potentiate other mitochondrial stressors, enhancing PINK1/Parkin-mediated mitophagy. These insights highlight important considerations for therapeutic strategies targeting mitophagy activation in Parkinson's disease.
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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.