ArticleActa pharmacologica Sinica2020
Somatic and germline mutations in the tumor suppressor gene PARK2 impair PINK1/Parkin-mediated mitophagy in lung cancer cells.
Article in Acta pharmacologica Sinica, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Mitophagy in cisplatin-induced kidney injury: regulatory mechanisms and therapeutic targets.Annals of medicine · 2026Review
- PPP2/PP2A-mediated dephosphorylation of LC3B links PINK1-PRKN/Parkin-mediated mitophagy to SCA12 pathogenesis.Autophagy · 2025Article
- Mitochondria-Associated Pathways in Cancer and Precancerous Conditions: Mechanistic Insights.International journal of molecular sciences · 2025Review
- Guanine monophosphate synthase-mediated nuclear and mitochondrial communication in the progression of gastric cancer.Translational cancer research · 2025Article
- Article
- Protective effects of olive oil against cardiac aging through mitophagy and apoptosis.Veterinary research forum : an international quarterly journal · 2025Article
- Amentoflavone regulates the miR-124-3p/CAPN2 axis to promote mitochondrial autophagy in HCC cells.Toxicology research · 2024Article
- Single nucleotide variants in lung cancer.Chinese medical journal pulmonary and critical care medicine · 2024Review
- ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating BCL2-BECN1 interaction.Acta pharmaceutica Sinica. B · 2024Article
- Genetic and pharmacologic p32-inhibition rescue CHCHD2-linked Parkinson's disease phenotypes in vivo and in cell models.Journal of biomedical science · 2024Article
- Insights into the role of mitophagy in lung cancer: current evidence and perspectives.Frontiers in pharmacology · 2024Review
- Insights from a Computational-Based Approach for Analyzing Autophagy Genes across Human Cancers.Genes · 2023Review
- Review
- Chlorpromazine affects autophagy in association with altered Rag GTPase-mTORC1-TFEB signaling.Frontiers in cell and developmental biology · 2023Article
- Increased mitophagy protects cochlear hair cells from aminoglycoside-induced damage.Autophagy · 2023Article
- Gefitinib facilitates PINK1/Parkin-mediated mitophagy by enhancing mitochondrial recruitment of OPTN.Fundamental research · 2022Article
- Kanglexin delays heart aging by promoting mitophagy.Acta pharmacologica Sinica · 2022Article
- Breast cancer: Muscarinic receptors as new targets for tumor therapy.World journal of clinical oncology · 2021Review
- Autophagy and organelle homeostasis in cancer.Developmental cell · 2021Review
- Deubiquitinase USP35 modulates ferroptosis in lung cancer via targeting ferroportin.Clinical and translational medicine · 2021Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PARK2, which encodes Parkin, is a disease-causing gene for both neurodegenerative disorders and cancer. Parkin can function as a neuroprotector that plays a crucial role in the regulation of mitophagy, and germline mutations in PARK2 are associated with Parkinson's disease (PD). Intriguingly, recent studies suggest that Parkin can also function as a tumor suppressor and that somatic and germline mutations in PARK2 are associated with various human cancers, including lung cancer. However, it is presently unknown how the tumor suppressor activity of Parkin is affected by these mutations and whether it is associated with mitophagy. Herein, we show that wild-type (WT) Parkin can rapidly translocate onto mitochondria following mitochondrial damage and that Parkin promotes mitophagic clearance of mitochondria in lung cancer cells. However, lung cancer-linked mutations inhibit the mitochondrial translocation and ubiquitin-associated activity of Parkin. Among all lung cancer-linked mutants that we tested, A46T Parkin failed to translocate onto mitochondria and could not recruit downstream mitophagic regulators, including optineurin (OPTN) and TFEB, whereas N254S and R275W Parkin displayed slower mitochondrial translocation than WT Parkin. Moreover, we found that deferiprone (DFP), an iron chelator that can induce mitophagy, greatly increased the death of A46T Parkin-expressing lung cancer cells. Taken together, our results reveal a novel mitophagic mechanism in lung cancer, suggesting that lung cancer-linked mutations in PARK2 are associated with impaired mitophagy and identifying DFP as a novel therapeutic agent for PARK2-linked lung cancer and possibly other types of cancers driven by mitophagic dysregulation.
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