Alterations in peroxisome-mitochondria interplay in skeletal muscle accelerate muscle dysfunction

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

doi:10.1038/s41467-025-64833-w

Alterations in peroxisome-mitochondria interplay in skeletal muscle accelerate muscle dysfunction

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^*

^*Corresponding author for this work

University of Padua
Venetian Institute of Molecular Medicine (VIMM)
National Research Council of Italy
University of Zurich
Amsterdam UMC
Fondazione Telethon
Institut des Maladies Métaboliques et Cardiovasculaires

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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.

Original language	English
Article number	9868
Journal	Nat. Commun.
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-64833-w
Publication status	Published - 1 Dec 2025

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Alterations-in-peroxisome-mitochondria-interplay-in-skeletal-muscle-accelerate-muscle-dysfunction.pdfFinal published version, 8.83 MBLicence: CC BY

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Scalabrin, M., Turco, E., Davigo, I., Filadi, R., Nogara, L., Gherardi, G., Barazzuol, L., Armani, A., Trani, G., Negro, S., Franco-Romero, A., Jaspers, Y., Baschiera, E., de Cegli, R., del Prete, E., Cali, T., Blaauw, B., Salviati, L., Rigoni, M., ... Romanello, V. (2025). Alterations in peroxisome-mitochondria interplay in skeletal muscle accelerate muscle dysfunction. Nat. Commun., 16(1), Article 9868. https://doi.org/10.1038/s41467-025-64833-w

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title = "Alterations in peroxisome-mitochondria interplay in skeletal muscle accelerate muscle dysfunction",

abstract = "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.",

author = "Marco Scalabrin and Eloisa Turco and Ilaria Davigo and Riccardo Filadi and Leonardo Nogara and Gaia Gherardi and Lucia Barazzuol and Andrea Armani and Giulia Trani and Samuele Negro and Anais Franco-Romero and Yorrick Jaspers and Elisa Baschiera and \{de Cegli\}, Rossella and \{del Prete\}, Eugenio and Tito Cali and Bert Blaauw and Leonardo Salviati and Michela Rigoni and Cristina Mammucari and Sylvie Caspar-Bauguil and Cedric Moro and Paola Pizzo and Marco Sandri and Stephan Kemp and Vanina Romanello",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

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doi = "10.1038/s41467-025-64833-w",

language = "English",

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Scalabrin, M, Turco, E, Davigo, I, Filadi, R, Nogara, L, Gherardi, G, Barazzuol, L, Armani, A, Trani, G, Negro, S, Franco-Romero, A, Jaspers, Y, Baschiera, E, de Cegli, R, del Prete, E, Cali, T, Blaauw, B, Salviati, L, Rigoni, M, Mammucari, C, Caspar-Bauguil, S, Moro, C, Pizzo, P, Sandri, M, Kemp, S & Romanello, V 2025, 'Alterations in peroxisome-mitochondria interplay in skeletal muscle accelerate muscle dysfunction', Nat. Commun., vol. 16, no. 1, 9868. https://doi.org/10.1038/s41467-025-64833-w

TY - JOUR

T1 - Alterations in peroxisome-mitochondria interplay in skeletal muscle accelerate muscle dysfunction

AU - Scalabrin, Marco

AU - Turco, Eloisa

AU - Davigo, Ilaria

AU - Filadi, Riccardo

AU - Nogara, Leonardo

AU - Gherardi, Gaia

AU - Barazzuol, Lucia

AU - Armani, Andrea

AU - Trani, Giulia

AU - Negro, Samuele

AU - Franco-Romero, Anais

AU - Jaspers, Yorrick

AU - Baschiera, Elisa

AU - de Cegli, Rossella

AU - del Prete, Eugenio

AU - Cali, Tito

AU - Blaauw, Bert

AU - Salviati, Leonardo

AU - Rigoni, Michela

AU - Mammucari, Cristina

AU - Caspar-Bauguil, Sylvie

AU - Moro, Cedric

AU - Pizzo, Paola

AU - Sandri, Marco

AU - Kemp, Stephan

AU - Romanello, Vanina

PY - 2025/12/1

Y1 - 2025/12/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/105021290176

U2 - 10.1038/s41467-025-64833-w

DO - 10.1038/s41467-025-64833-w

M3 - Article

C2 - 41213899

SN - 2041-1723

VL - 16

JO - Nat. Commun.

JF - Nat. Commun.

IS - 1

M1 - 9868

ER -

Alterations in peroxisome-mitochondria interplay in skeletal muscle accelerate muscle dysfunction

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