%0 Journal Article
%A Coppa, Andrea
%A Guha, Sanjib
%A Fourcade, Stéphane
%A Parameswaran, Janani
%A Ruiz, Montserrat
%A Moser, Ann B
%A Schlüter, Agatha
%A Murphy, Michael P
%A Lizcano, Jose Miguel
%A Miranda-Vizuete, Antonio
%A Dalfó, Esther
%A Pujol, Aurora
%T The peroxisomal fatty acid transporter ABCD1/PMP-4 is required in the C. elegans hypodermis for axonal maintenance: A worm model for adrenoleukodystrophy.
%D 2020
%U http://hdl.handle.net/10668/15041
%X Adrenoleukodystrophy 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.
%K Axonal degeneration
%K Hypodermis
%K Lipid droplets
%K Mitochondria redox imbalance
%K Peroxisomes
%K X-linked adrenoleukodystrophy
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