The mitochondrial-related defects in WDR45-defective cells and how to reverse them
Awardee: Mario Mauthe
Institution: University Medical Center Groningen (UMCG)
Grant Amount: $60,000.00
Funding Period: February 1, 2024 - January 31, 2025
Summary:
The WDR45 gene, which when mutated causes BPAN, produces a protein called WDR45. WDR45 is involved in autophagy, a process that is responsible for removing damaged cellular components. Furthermore, we have observed that the mutated WDR45 protein also affects critical cellular structures called mitochondria, which play vital roles in energy production and metabolism regulation. Similar malfunctioning of mitochondria is also observed in several BPAN-related diseases (other NBIA subtypes) such as PKAN, CoPan, PLAN and MPAN. Within this project, our team will investigate how mutations in WDR45 affects the mitochondria and thereby contribute to the BPAN pathology. Our final goal is to reverse the changes in mitochondria, which are caused by the mutated WDR45 protein, using pharmaceutical compounds. We will start working in cellular model systems, and then move to validating our findings in BPAN patient-derived cells.