RT Journal Article
T1 The peroxisomal fatty acid transporter ABCD1/PMP-4 is required in the C. elegans hypodermis for axonal maintenance: A worm model for adrenoleukodystrophy.
A1 Coppa, Andrea
A1 Guha, Sanjib
A1 Fourcade, Stéphane
A1 Parameswaran, Janani
A1 Ruiz, Montserrat
A1 Moser, Ann B
A1 Schlüter, Agatha
A1 Murphy, Michael P
A1 Lizcano, Jose Miguel
A1 Miranda-Vizuete, Antonio
A1 Dalfó, Esther
A1 Pujol, Aurora
K1 Axonal degeneration
K1 Hypodermis
K1 Lipid droplets
K1 Mitochondria redox imbalance
K1 Peroxisomes
K1 X-linked adrenoleukodystrophy
AB 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.
YR 2020
FD 2020-02-01
LK http://hdl.handle.net/10668/15041
UL http://hdl.handle.net/10668/15041
LA en
DS RISalud
RD Apr 11, 2025