Alterations in peroxisome-mitochondria interplay in skeletal muscle accelerate muscle dysfunction
Year: 2025
Type: article
Abstract: ABSTRACT Whole-body energy expenditure, as well as glucose and lipid metabolism, are regulated by skeletal muscles, which account for 40-50% of human body mass. Peroxisomes are dynamic organelles that play a crucial role in lipid metabolism and clearance of reactive oxygen species, however their role in muscles remains poorly understood. To clarify this issue, we generated a muscle-specific transgenic mouse line with peroxisome import deficiency resulting from deletion of peroxisomal biogenesis factor 5 (Pex5). Pex5 inhibition disrupted the tethering between peroxisomes and mitochondria, impaired lipid metabolism and reduced muscle force and exercise performance. Moreover, mitochondrial content and function were also altered, accelerating age-related structural defects, neuromuscular junction degeneration, and muscle atrophy. Altogether, our findings show the importance of preserving peroxisomal function and their contact sites with mitochondria to maintain muscle health during aging.
Source: Nature Communications
Authors: Marco Scalabrin, Eloisa Turco, Ilaria Davigo, Riccardo Filadi, Leonardo Nogara, Gaia Gherardi, Lucia Barazzuol, Andrea Armani, Giulia Trani, Samuele Negro, Anais Franco-Romero, Yorrick Jaspers, Elisa Baschiera, Rossella De Cegli, Eugenio Del Prete, Tito Cali, Bert Blaauw, Leonardo Salviati, Michela Rigoni, Cristina Mammucari, Sylvie Caspar-Bauguil, Cedric Moro, Paola Pizzo, Marco Sandri, Stephan Kemp, Vanina Romanello
Institutions: University of Padua, Veneto Institute of Molecular Medicine, National Research Council, University of Zurich, Azienda Ospedale - Università Padova, Amsterdam University Medical Centers, Amsterdam Gastroenterology Endocrinology Metabolism, Telethon Institute Of Genetics And Medicine, Inserm, Institut des Maladies Métaboliques et Cardiovasculaires, Université de Toulouse
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W4416092365