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Lookup NU author(s): Elena Martoni, Professor Hanns Lochmuller, Professor Volker StraubORCiD, Emerita Professor Katherine Bushby
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Collagen VI myopathies are genetic disorders caused by mutations in collagen 6 A1, A2 and A3 genes, ranging from the severe Ullrich congenital muscular dystrophy to the milder Bethlem myopathy, which is recapitulated by collagen-VI-null (Col6a1(-/-)) mice. Abnormalities in mitochondria and autophagic pathway have been proposed as pathogenic causes of collagen VI myopathies, but the link between collagen VI defects and these metabolic circuits remains unknown. To unravel the expression profiling perturbation in muscles with collagen VI myopathies, we performed a deep RNA profiling in both Col6a1(-/-) mice and patients with collagen VI pathology. The interactome map identified common pathways suggesting a previously undetected connection between circadian genes and collagen VI pathology. Intriguingly, Bmal1(-/-) (also known as Arntl) mice, a well-characterized model displaying arrhythmic circadian rhythms, showed profound deregulation of the collagen VI pathway and of autophagy-related genes. The involvement of circadian rhythms in collagen VI myopathies is new and links autophagy and mitochondrial abnormalities. It also opens new avenues for therapies of hereditary myopathies to modulate the molecular clock or potential gene-environment interactions that might modify muscle damage pathogenesis.
Author(s): Scotton C, Bovolenta M, Schwartz E, Falzarano MS, Martoni E, Passarelli C, Armaroli A, Osman H, Rodolico C, Messina S, Pegoraro E, D'Amico A, Bertini E, Gualandi F, Neri M, Selvatici R, Boffi P, Maioli MA, Lochmuller H, Straub V, Bushby K, Castrignano T, Pesole G, Sabatelli P, Merlini L, Braghetta P, Bonaldo P, Bernardi P, Foley R, Cirak S, Zaharieva I, Muntoni F, Capitanio D, Gelfi C, Kotelnikova E, Yuryev A, Lebowitz M, Zhang XP, Hodge BA, Esser KA, Ferlini A
Publication type: Article
Publication status: Published
Journal: Journal of Cell Science
Year: 2016
Volume: 129
Issue: 8
Pages: 1671-1684
Print publication date: 15/04/2016
Online publication date: 04/03/2016
Acceptance date: 16/02/2016
ISSN (print): 0021-9533
ISSN (electronic): 1477-9137
Publisher: The Company of Biologists Ltd
URL: http://dx.doi.org/10.1242/jcs.175927
DOI: 10.1242/jcs.175927
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