Coppa, AndreaGuha, SanjibFourcade, StéphaneParameswaran, JananiRuiz, MontserratMoser, Ann BSchlüter, AgathaMurphy, Michael PLizcano, Jose MiguelMiranda-Vizuete, AntonioDalfó, EstherPujol, Aurora2023-02-082023-02-082020-02-01http://hdl.handle.net/10668/15041Adrenoleukodystrophy is a neurometabolic disorder caused by a defective peroxisomal ABCD1 transporter of very long-chain fatty acids (VLCFAs). Its pathogenesis is incompletely understood. Here we characterize a nematode model of X-ALD with loss of the pmp-4 gene, the worm orthologue of ABCD1. These mutants recapitulate the hallmarks of X-ALD: i) VLCFAs accumulation and impaired mitochondrial redox homeostasis and ii) axonal damage coupled to locomotor dysfunction. Furthermore, we identify a novel role for PMP-4 in modulating lipid droplet dynamics. Importantly, we show that the mitochondria targeted antioxidant MitoQ normalizes lipid droplets size, and prevents axonal degeneration and locomotor disability, highlighting its therapeutic potential. Moreover, PMP-4 acting solely in the hypodermis rescues axonal and locomotion abnormalities, suggesting a myelin-like role for the hypodermis in providing essential peroxisomal functions for the nematode nervous system.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Axonal degenerationHypodermisLipid dropletsMitochondria redox imbalancePeroxisomesX-linked adrenoleukodystrophyATP Binding Cassette Transporter, Subfamily D, Member 1ATP-Binding Cassette TransportersAdrenoleukodystrophyAnimalsCaenorhabditis elegansFatty AcidsMiceMice, KnockoutSubcutaneous Tissueresearch article32017990open access10.1016/j.freeradbiomed.2020.01.1771873-4596PMC7611262http://diposit.ub.edu/dspace/bitstream/2445/154018/1/Coppa2020.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611262/pdf