Aerobic and resistance exercise-regulated phosphoproteome and acetylproteome modifications in human skeletal muscle

Abstract Despite indisputable benefits of different exercise modes, the molecular underpinnings of their divergent responses remain unclear. We investigate post-translational modifications in human skeletal muscle following 12 weeks of high-intensity aerobic interval or resistance exercise training....

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Main Authors: Mark W. Pataky, Carrie J. Heppelmann, Kyle J. Sevits, Aneesh K. Asokan, Arathi Prabha Kumar, Katherine A. Klaus, Surendra Dasari, Hawley E. Kunz, Matthew D. Strub, Matthew M. Robinson, Joshua J. Coon, Ian R. Lanza, Christopher M. Adams, K. Sreekumaran Nair
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60049-0
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author Mark W. Pataky
Carrie J. Heppelmann
Kyle J. Sevits
Aneesh K. Asokan
Arathi Prabha Kumar
Katherine A. Klaus
Surendra Dasari
Hawley E. Kunz
Matthew D. Strub
Matthew M. Robinson
Joshua J. Coon
Ian R. Lanza
Christopher M. Adams
K. Sreekumaran Nair
author_facet Mark W. Pataky
Carrie J. Heppelmann
Kyle J. Sevits
Aneesh K. Asokan
Arathi Prabha Kumar
Katherine A. Klaus
Surendra Dasari
Hawley E. Kunz
Matthew D. Strub
Matthew M. Robinson
Joshua J. Coon
Ian R. Lanza
Christopher M. Adams
K. Sreekumaran Nair
author_sort Mark W. Pataky
collection DOAJ
description Abstract Despite indisputable benefits of different exercise modes, the molecular underpinnings of their divergent responses remain unclear. We investigate post-translational modifications in human skeletal muscle following 12 weeks of high-intensity aerobic interval or resistance exercise training. High-intensity aerobic training induces acetylproteome modifications including several mitochondrial proteins, indicating post-translational regulation of energetics machinery, whereas resistance exercise training regulates phosphoproteomic modifications of contractile/cytoskeletal machinery, consistent with greater strength. Furthermore, despite similar transcriptional responses to a single acute bout of aerobic and resistance exercise, more robust phosphoproteomic and metabolomic responses occur with acute aerobic exercise, including phosphorylation of structural/contractile and membrane transport machinery, and the nascent polypeptide-associated complex-α, a regulator of protein translation. Together, our findings provide new insight on the intricate phosphoproteomic and acetylproteomic modifications in muscle that potentially explain physiological responses to different modes of chronic and acute exercise. This study is registered with ClinicalTrials.gov, numbers NCT01477164 and NCT04158375.
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spelling doaj-art-39d2700ebf0c4a5887d7d27f6d06f9f52025-08-20T03:37:37ZengNature PortfolioNature Communications2041-17232025-07-0116111910.1038/s41467-025-60049-0Aerobic and resistance exercise-regulated phosphoproteome and acetylproteome modifications in human skeletal muscleMark W. Pataky0Carrie J. Heppelmann1Kyle J. Sevits2Aneesh K. Asokan3Arathi Prabha Kumar4Katherine A. Klaus5Surendra Dasari6Hawley E. Kunz7Matthew D. Strub8Matthew M. Robinson9Joshua J. Coon10Ian R. Lanza11Christopher M. Adams12K. Sreekumaran Nair13Division of Endocrinology and Metabolism, Mayo ClinicDivision of Endocrinology and Metabolism, Mayo ClinicDivision of Endocrinology and Metabolism, Mayo ClinicDivision of Endocrinology and Metabolism, Mayo ClinicDivision of Endocrinology and Metabolism, Mayo ClinicDivision of Endocrinology and Metabolism, Mayo ClinicDepartment of Quantitative Health Sciences, Mayo ClinicDivision of Endocrinology and Metabolism, Mayo ClinicDivision of Endocrinology and Metabolism, Mayo ClinicSchool of Exercise, Sport, and Health Sciences, College of Health, Oregon State UniversityDepartment of Chemistry, University of Wisconsin-MadisonDivision of Endocrinology and Metabolism, Mayo ClinicDivision of Endocrinology and Metabolism, Mayo ClinicDivision of Endocrinology and Metabolism, Mayo ClinicAbstract Despite indisputable benefits of different exercise modes, the molecular underpinnings of their divergent responses remain unclear. We investigate post-translational modifications in human skeletal muscle following 12 weeks of high-intensity aerobic interval or resistance exercise training. High-intensity aerobic training induces acetylproteome modifications including several mitochondrial proteins, indicating post-translational regulation of energetics machinery, whereas resistance exercise training regulates phosphoproteomic modifications of contractile/cytoskeletal machinery, consistent with greater strength. Furthermore, despite similar transcriptional responses to a single acute bout of aerobic and resistance exercise, more robust phosphoproteomic and metabolomic responses occur with acute aerobic exercise, including phosphorylation of structural/contractile and membrane transport machinery, and the nascent polypeptide-associated complex-α, a regulator of protein translation. Together, our findings provide new insight on the intricate phosphoproteomic and acetylproteomic modifications in muscle that potentially explain physiological responses to different modes of chronic and acute exercise. This study is registered with ClinicalTrials.gov, numbers NCT01477164 and NCT04158375.https://doi.org/10.1038/s41467-025-60049-0
spellingShingle Mark W. Pataky
Carrie J. Heppelmann
Kyle J. Sevits
Aneesh K. Asokan
Arathi Prabha Kumar
Katherine A. Klaus
Surendra Dasari
Hawley E. Kunz
Matthew D. Strub
Matthew M. Robinson
Joshua J. Coon
Ian R. Lanza
Christopher M. Adams
K. Sreekumaran Nair
Aerobic and resistance exercise-regulated phosphoproteome and acetylproteome modifications in human skeletal muscle
Nature Communications
title Aerobic and resistance exercise-regulated phosphoproteome and acetylproteome modifications in human skeletal muscle
title_full Aerobic and resistance exercise-regulated phosphoproteome and acetylproteome modifications in human skeletal muscle
title_fullStr Aerobic and resistance exercise-regulated phosphoproteome and acetylproteome modifications in human skeletal muscle
title_full_unstemmed Aerobic and resistance exercise-regulated phosphoproteome and acetylproteome modifications in human skeletal muscle
title_short Aerobic and resistance exercise-regulated phosphoproteome and acetylproteome modifications in human skeletal muscle
title_sort aerobic and resistance exercise regulated phosphoproteome and acetylproteome modifications in human skeletal muscle
url https://doi.org/10.1038/s41467-025-60049-0
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