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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 Capella, Esther Pujol Onofre, Aurora |
Keywords: | Trastorns del metabolisme Peroxisomes Disorders of metabolism Peroxisomes |
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: https://doi.org/10.1016/j.freeradbiomed.2020.01.177 |
It is part of: | Free Radical Biology and Medicine, 2020 |
URI: | http://hdl.handle.net/2445/154018 |
Related resource: | https://doi.org/10.1016/j.freeradbiomed.2020.01.177 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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Coppa2020.pdf | 3.92 MB | Adobe PDF | View/Open |
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