Alterations in peroxisome-mitochondria interplay in skeletal muscle accelerate muscle dysfunction
Skeletal muscles, which constitute 40-50% of body mass, regulate whole-body energy expenditure and glucose and lipid metabolism. Peroxisomes are dynamic organelles that play a crucial role in lipid metabolism and clearance of reactive oxygen species, however their role in skeletal muscle remains poorly understood. To clarify this issue, we generated a muscle-specific transgenic mouse line with peroxisome import deficiency through the deletion of peroxisomal biogenesis factor 5 (Pex5). Here, we show that Pex5 inhibition results in impaired lipid metabolism, reduced muscle force and exercise performance. Moreover, mitochondrial structure, content, and function are also altered, accelerating the onset of age-related structural defects, neuromuscular junction degeneration, and muscle atrophy. Consistent with these observations, we observe a decline in peroxisomal content in the muscles of control mice undergoing natural aging. Altogether, our findings show the importance of preserving peroxisomal function and their interplay with mitochondria to maintain muscle health during aging.
Authors
- Yorrick Jaspers (ORCID: https://orcid.org/0000-0002-9153-5734)
- E Turco (ORCID: https://orcid.org/0009-0007-5948-7668)
- Stephan Kemp (ORCID: https://orcid.org/0000-0003-2023-064X)
- Vanina Romanello (ORCID: https://orcid.org/0000-0002-7712-6416)
- Samuele Negro (ORCID: https://orcid.org/0000-0002-8038-1696)
- Anaïs Franco‐Romero (ORCID: https://orcid.org/0000-0002-2792-1200)
- Michela Rigoni (ORCID: https://orcid.org/0000-0003-1763-2648)
- Paola Pizzo (ORCID: https://orcid.org/0000-0001-6077-3265)
- Cédric Moro (ORCID: https://orcid.org/0000-0003-4294-0597)
- Giulia Trani (ORCID: https://orcid.org/0000-0003-4289-1799)
- Bert Blaauw (ORCID: https://orcid.org/0000-0002-4167-5106)
- Riccardo Filadi (ORCID: https://orcid.org/0000-0002-5871-2620)
- Gaia Gherardi (ORCID: https://orcid.org/0000-0001-6212-3477)
- Sylvie Caspar‐Bauguil (ORCID: https://orcid.org/0000-0003-2682-0704)
- Elisa Baschiera
- Marco Sandri (ORCID: https://orcid.org/0000-0001-8509-7558)
- Eugenio Del Prete (ORCID: https://orcid.org/0000-0003-3214-9021)
- Leonardo Nogara (ORCID: https://orcid.org/0000-0002-7009-8707)
- Tito Calí (ORCID: https://orcid.org/0000-0002-8901-1659)
- Lucia Barazzuol (ORCID: https://orcid.org/0000-0002-7569-9704)
- Cristina Mammucari (ORCID: https://orcid.org/0000-0003-3220-9610)
- Marco Scalabrin
- Andrea Armani (ORCID: https://orcid.org/0000-0002-4765-9748)
- Leonardo Salviati (ORCID: https://orcid.org/0000-0001-5642-9963)
- Rossella De Cegli (ORCID: https://orcid.org/0000-0002-8526-8692)
- Ilaria Davigo
Institutions
- University of Padua (IT)
- Inserm (FR)
- University of Zurich (CH)
- Veneto Institute of Molecular Medicine (IT)
- Institut des Maladies Métaboliques et Cardiovasculaires (FR)
- Telethon Institute Of Genetics And Medicine (IT)
- National Research Council (IT)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-10
- DOI
- https://doi.org/10.1038/s41467-025-64833-w
- Citations
- 1
- Primary Topic
- Peroxisome Proliferator-Activated Receptors
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- European Commission