Lipid hydroperoxides promote sarcopenia through carbonyl stress

Hiroaki Eshima; Justin L. Shahtout; Piyarat Siripoksup; MacKenzie J. Pearson; Ziad S. Mahmassani; Patrick J. Ferrara; Alexis W. Lyons; John Alan Maschek; Alek D. Peterlin; Anthony R.P. Verkerke; Jordan M. Johnson; Anahy Salcedo; Jonathan J. Petrocelli; Edwin R. Miranda; Ethan J. Anderson; Sihem Boudina; Qitao Ran; James E. Cox; Micah J. Drummond; Katsuhiko Funai

doi:10.7554/eLife.85289

Lipid hydroperoxides promote sarcopenia through carbonyl stress

Hiroaki Eshima, Justin L. Shahtout, Piyarat Siripoksup, MacKenzie J. Pearson, Ziad S. Mahmassani, Patrick J. Ferrara, Alexis W. Lyons, John Alan Maschek, Alek D. Peterlin, Anthony R.P. Verkerke, Jordan M. Johnson, Anahy Salcedo, Jonathan J. Petrocelli, Edwin R. Miranda, Ethan J. Anderson, Sihem Boudina, Qitao Ran, James E. Cox, Micah J. Drummond, Katsuhiko Funai

Department of Cell Systems & Anatomy

Producción científica: Article › revisión exhaustiva

13 Citas (Scopus)

Resumen

Reactive oxygen species (ROS) accumulation is a cardinal feature of skeletal muscle atrophy. ROS refers to a collection of radical molecules whose cellular signals are vast, and it is unclear which downstream consequences of ROS are responsible for the loss of muscle mass and strength. Here, we show that lipid hydroperoxides (LOOH) are increased with age and disuse, and the accumulation of LOOH by deletion of glutathione peroxidase 4 (GPx4) is sufficient to augment muscle atrophy. LOOH promoted atrophy in a lysosomal-dependent, proteasomal-independent manner. In young and old mice, genetic and pharmacological neutralization of LOOH or their secondary reactive lipid aldehydes robustly prevented muscle atrophy and weakness, indicating that LOOH-derived carbonyl stress mediates age- and disuse-induced muscle dysfunction. Our findings provide novel insights for the role of LOOH in sarcopenia including a therapeutic implication by pharmacological suppression.

Idioma original	English (US)
Publicación	eLife
Volumen	12
DOI	https://doi.org/10.7554/eLife.85289
Estado	Published - mar 23 2023

ASJC Scopus subject areas

General Neuroscience
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology

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Eshima, H., Shahtout, J. L., Siripoksup, P., Pearson, M. J., Mahmassani, Z. S., Ferrara, P. J., Lyons, A. W., Maschek, J. A., Peterlin, A. D., Verkerke, A. R. P., Johnson, J. M., Salcedo, A., Petrocelli, J. J., Miranda, E. R., Anderson, E. J., Boudina, S., Ran, Q., Cox, J. E., Drummond, M. J., & Funai, K. (2023). Lipid hydroperoxides promote sarcopenia through carbonyl stress. eLife, 12. https://doi.org/10.7554/eLife.85289

Eshima, H, Shahtout, JL, Siripoksup, P, Pearson, MJ, Mahmassani, ZS, Ferrara, PJ, Lyons, AW, Maschek, JA, Peterlin, AD, Verkerke, ARP, Johnson, JM, Salcedo, A, Petrocelli, JJ, Miranda, ER, Anderson, EJ, Boudina, S, Ran, Q, Cox, JE, Drummond, MJ & Funai, K 2023, 'Lipid hydroperoxides promote sarcopenia through carbonyl stress', eLife, vol. 12. https://doi.org/10.7554/eLife.85289

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title = "Lipid hydroperoxides promote sarcopenia through carbonyl stress",

abstract = "Reactive oxygen species (ROS) accumulation is a cardinal feature of skeletal muscle atrophy. ROS refers to a collection of radical molecules whose cellular signals are vast, and it is unclear which downstream consequences of ROS are responsible for the loss of muscle mass and strength. Here, we show that lipid hydroperoxides (LOOH) are increased with age and disuse, and the accumulation of LOOH by deletion of glutathione peroxidase 4 (GPx4) is sufficient to augment muscle atrophy. LOOH promoted atrophy in a lysosomal-dependent, proteasomal-independent manner. In young and old mice, genetic and pharmacological neutralization of LOOH or their secondary reactive lipid aldehydes robustly prevented muscle atrophy and weakness, indicating that LOOH-derived carbonyl stress mediates age- and disuse-induced muscle dysfunction. Our findings provide novel insights for the role of LOOH in sarcopenia including a therapeutic implication by pharmacological suppression.",

keywords = "cell biology, lipid peroxidation, mouse, muscle atrophy, oxidative stress, sarcopenia, skeletal muscle",

author = "Hiroaki Eshima and Shahtout, {Justin L.} and Piyarat Siripoksup and Pearson, {MacKenzie J.} and Mahmassani, {Ziad S.} and Ferrara, {Patrick J.} and Lyons, {Alexis W.} and Maschek, {John Alan} and Peterlin, {Alek D.} and Verkerke, {Anthony R.P.} and Johnson, {Jordan M.} and Anahy Salcedo and Petrocelli, {Jonathan J.} and Miranda, {Edwin R.} and Anderson, {Ethan J.} and Sihem Boudina and Qitao Ran and Cox, {James E.} and Drummond, {Micah J.} and Katsuhiko Funai",

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year = "2023",

month = mar,

day = "23",

doi = "10.7554/eLife.85289",

language = "English (US)",

volume = "12",

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T1 - Lipid hydroperoxides promote sarcopenia through carbonyl stress

AU - Eshima, Hiroaki

AU - Shahtout, Justin L.

AU - Siripoksup, Piyarat

AU - Pearson, MacKenzie J.

AU - Mahmassani, Ziad S.

AU - Ferrara, Patrick J.

AU - Lyons, Alexis W.

AU - Maschek, John Alan

AU - Peterlin, Alek D.

AU - Verkerke, Anthony R.P.

AU - Johnson, Jordan M.

AU - Salcedo, Anahy

AU - Petrocelli, Jonathan J.

AU - Miranda, Edwin R.

AU - Anderson, Ethan J.

AU - Boudina, Sihem

AU - Ran, Qitao

AU - Cox, James E.

AU - Drummond, Micah J.

AU - Funai, Katsuhiko

PY - 2023/3/23

Y1 - 2023/3/23

N2 - Reactive oxygen species (ROS) accumulation is a cardinal feature of skeletal muscle atrophy. ROS refers to a collection of radical molecules whose cellular signals are vast, and it is unclear which downstream consequences of ROS are responsible for the loss of muscle mass and strength. Here, we show that lipid hydroperoxides (LOOH) are increased with age and disuse, and the accumulation of LOOH by deletion of glutathione peroxidase 4 (GPx4) is sufficient to augment muscle atrophy. LOOH promoted atrophy in a lysosomal-dependent, proteasomal-independent manner. In young and old mice, genetic and pharmacological neutralization of LOOH or their secondary reactive lipid aldehydes robustly prevented muscle atrophy and weakness, indicating that LOOH-derived carbonyl stress mediates age- and disuse-induced muscle dysfunction. Our findings provide novel insights for the role of LOOH in sarcopenia including a therapeutic implication by pharmacological suppression.

AB - Reactive oxygen species (ROS) accumulation is a cardinal feature of skeletal muscle atrophy. ROS refers to a collection of radical molecules whose cellular signals are vast, and it is unclear which downstream consequences of ROS are responsible for the loss of muscle mass and strength. Here, we show that lipid hydroperoxides (LOOH) are increased with age and disuse, and the accumulation of LOOH by deletion of glutathione peroxidase 4 (GPx4) is sufficient to augment muscle atrophy. LOOH promoted atrophy in a lysosomal-dependent, proteasomal-independent manner. In young and old mice, genetic and pharmacological neutralization of LOOH or their secondary reactive lipid aldehydes robustly prevented muscle atrophy and weakness, indicating that LOOH-derived carbonyl stress mediates age- and disuse-induced muscle dysfunction. Our findings provide novel insights for the role of LOOH in sarcopenia including a therapeutic implication by pharmacological suppression.

KW - cell biology

KW - lipid peroxidation

KW - mouse

KW - muscle atrophy

KW - oxidative stress

KW - sarcopenia

KW - skeletal muscle

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JO - eLife

JF - eLife

ER -

Lipid hydroperoxides promote sarcopenia through carbonyl stress

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ASJC Scopus subject areas

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