ArticleInternational journal of molecular sciences2022
Mutant WDR45 Leads to Altered Ferritinophagy and Ferroptosis in β-Propeller Protein-Associated Neurodegeneration.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Functional Homology of WIPI4 and Atg18 EnablesInternational journal of molecular sciences · 2026Article
- Review
- Metal ion dyshomeostasis in neurological disorders: from pathological mechanisms to targeted neuroprotective and regenerative strategies.Frontiers in pharmacology · 2026Review
- Mutations in the Key Autophagy Tethering Factor EPG5 Link Neurodevelopmental and Neurodegenerative Disorders Including Early-Onset Parkinsonism.Annals of neurology · 2025Article
- Autophagy regulator ATG5 preserves cerebellar function by safeguarding its glycolytic activity.Nature metabolism · 2025Article
- An update on autophagy disorders.Journal of inherited metabolic disease · 2025Review
- Ferritin Hinders Ferroptosis in Non-Tumorous Diseases: Regulatory Mechanisms and Potential Consequences.Current protein & peptide science · 2025Review
- Iron Dyshomeostasis in Neurodegeneration with Brain Iron Accumulation (NBIA): Is It the Cause or the Effect?Cells · 2024Review
- Regulating NCOA4-Mediated Ferritinophagy for Therapeutic Intervention in Cerebral Ischemia-Reperfusion Injury.Neurochemical research · 2024Article
- Iron imbalance in neurodegeneration.Molecular psychiatry · 2024Review
- Loss of WIPI4 in neurodegeneration causes autophagy-independent ferroptosis.Nature cell biology · 2024Article
- Lipid droplet accumulation in Wdr45-deficient cells caused by impairment of chaperone-mediated autophagic degradation of Fasn.Lipids in health and disease · 2024Article
- A burning question from the first international BPAN symposium: is restoration of autophagy a promising therapeutic strategy for BPAN?Autophagy · 2023Article
- The mechanism of ferroptosis and its related diseases.Molecular biomedicine · 2023Review
- Antioxidants Prevent Iron Accumulation and Lipid Peroxidation, but Do Not Correct Autophagy Dysfunction or Mitochondrial Bioenergetics in Cellular Models of BPAN.International journal of molecular sciences · 2023Article
- The Expanding Phenotypical Spectrum ofGenes · 2023Review
- Not to Miss: Intronic Variants, Treatment, and Review of the Phenotypic Spectrum inInternational journal of molecular sciences · 2023Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Beta-propeller protein-associated neurodegeneration (BPAN) is a subtype of neurodegeneration with brain iron accumulation (NBIA) caused by loss-of-function variants in WDR45. The underlying mechanism of iron accumulation in WDR45 deficiency remains elusive. We established a primary skin fibroblast culture of a new BPAN patient with a missense variant p.(Asn61Lys) in WDR45 (NM_007075.3: c.183C>A). The female patient has generalized dystonia, anarthria, parkinsonism, spasticity, stereotypies, and a distinctive cranial MRI with generalized brain atrophy, predominantly of the cerebellum. For the functional characterization of this variant and to provide a molecular link of WDR45 and iron accumulation, we looked for disease- and variant-related changes in the patient’s fibroblasts by qPCR, immunoblotting and immunofluorescence comparing to three controls and a previously reported WDR45 patient. We demonstrated molecular changes in mutant cells comprising an impaired mitochondrial network, decreased levels of lysosomal proteins and enzymes, and altered autophagy, confirming the pathogenicity of the variant. Compared to increased levels of the ferritinophagy marker Nuclear Coactivator 4 (NCOA4) in control cells upon iron treatment, patients’ cells revealed unchanged NCOA4 protein levels, indicating disturbed ferritinophagy. Additionally, we observed abnormal protein levels of markers of the iron-dependent cell death ferroptosis in patients’ cells. Altogether, our data suggests that WDR45 deficiency affects ferritinophagy and ferroptosis, consequentially disturbing iron recycling.
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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.