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Title: The peroxisomal fatty acid transporter ABCD1/PMP-4 is required in the C. elegans hypodermis for axonal maintenance: A worm model for adrenoleukodystrophy
Author: Coppa, Andrea
Guha, Sanjib
Fourcade, Stéphane
Parameswaran, Janani
Ruiz, Montserrat
Moser, Ann B.
Schlüter, Agatha
Murphy, Michael P.
Lizcano, José Miguel
Miranda Vizuete, Antonio
Dalfó, Esther
Pujol Onofre, Aurora
Keywords: Trastorns del metabolisme
Disorders of metabolism
Issue Date: 1-Feb-2020
Publisher: Elsevier BV
Abstract: 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.
Note: Versió postprint del document publicat a:
It is part of: Free Radical Biology and Medicine, 2020
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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