Regulation of mitophagy by the NSL complex underlies genetic risk for Parkinson’s disease at 16q11.2 and MAPT H1 loci
Published July 29, 2022
Output Details
Preprint January 7, 2020
Published July 29, 2022
Description
Impaired mitophagy is a key causative pathway in familial Parkinson’s disease, but its relevance to idiopathic Parkinson’s disease is unclear. We used a mitophagy screening assay to evaluate the functional significance of risk genes identified through genome-wide association studies. We identified two new regulators of PINK1-dependent mitophagy initiation, KAT8 and KANSL1, previously shown to modulate lysine acetylation. These findings suggest PINK1-mitophagy is a contributing factor to idiopathic Parkinson’s disease. KANSL1 is located on chromosome 17q21 where the risk associated gene has long been considered to be MAPT. While our data do not exclude a possible association between the MAPT gene and Parkinson’s disease, they provide strong evidence that KANSL1 plays a crucial role in the disease. Finally, these results enrich our understanding of physiological events regulating mitophagy and establish a novel pathway for drug targeting in neurodegeneration. Article published in Brain on 08 September 2022. Initial Preprint doi: 10.1101/2020.01.06.896241 posted on 30 July 2021 (prior to ASAP funds being used).
Identifier (DOI)
10.1093/brain/awac325
