Sprint interval exercise disrupts mitochondrial ultrastructure driving a unique mitochondrial stress response and remodelling in men
Exercise is a key lifestyle intervention for mitochondrial health, yet the molecular mechanisms by which different exercise prescriptions regulate mitochondrial remodeling remain unclear. We conducted an open-label counterbalanced randomized controlled trial (ACTRN12617001105336) and observed that sprint-interval exercise (SIE; n = 14), compared to moderate-intensity continuous exercise (MICE; n = 14), induces a mitochondrial stress signature and unfolded protein response (UPR<sup>mt</sup>). SIE triggers morphological and structural mitochondrial alterations along with activation of the integrated stress response (ISR) and mitochondrial quality control (MQC) pathways. Following eight weeks of training, moderate-intensity continuous training (MICT) increases mitochondrial content, complex I activity, and displays an enrichment of tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) proteins, while sprint-interval training (SIT) improves respiratory function and upregulates pathways involved in 1-carbon metabolism and protein quality control. We identify COX7A2L accumulating in III<sub>2</sub> + IV<sub>1</sub> supercomplexes only after SIT. These findings elucidate how exercise intensity shapes mitochondrial remodeling, informing tailored exercise prescriptions.
Authors
- Nicholas A. Jamnick (ORCID: https://orcid.org/0000-0003-0890-2853)
- Dale F. Taylor (ORCID: https://orcid.org/0000-0001-6766-6948)
- Georg Ramm (ORCID: https://orcid.org/0000-0003-3596-2288)
- Javier Botella (ORCID: https://orcid.org/0000-0001-9722-8519)
- David A. Stroud (ORCID: https://orcid.org/0000-0002-2048-3383)
- Cristina Ugalde (ORCID: https://orcid.org/0000-0002-9742-1877)
- Javier Díaz‐Lara (ORCID: https://orcid.org/0000-0003-1970-6313)
- Nicholas J. Saner (ORCID: https://orcid.org/0000-0002-6011-7126)
- Viola Oorschot (ORCID: https://orcid.org/0000-0002-8122-8271)
- Erika Fernández‐Vizarra (ORCID: https://orcid.org/0000-0002-2469-142X)
- David John Bishop (ORCID: https://orcid.org/0000-0002-6956-9188)
- Michael Lazarou (ORCID: https://orcid.org/0000-0003-2150-5545)
- Michele Brischigliaro (ORCID: https://orcid.org/0000-0003-1520-1342)
- Andrew Garnham (ORCID: https://orcid.org/0000-0001-8068-9300)
- Nikeisha J. Caruana (ORCID: https://orcid.org/0000-0002-0817-1686)
- Sandra López-Calcerrada (ORCID: https://orcid.org/0000-0002-0385-8067)
- Enrico Perri (ORCID: https://orcid.org/0000-0002-7869-6365)
Institutions
- Royal Children's Hospital (AU)
- Consejo Superior de Investigaciones Científicas (ES)
- University of Padua (IT)
- University of Miami (US)
- Deakin University (AU)
- The University of Melbourne (AU)
- University of Milan (IT)
- Walter and Eliza Hall Institute of Medical Research (AU)
- Universidad de Zaragoza (ES)
- Australian Regenerative Medicine Institute (AU)
- Research Institute Hospital 12 de Octubre (ES)
- Veneto Institute of Molecular Medicine (IT)
- Victorian Clinical Genetics Services (AU)
- Centre for Biomedical Network Research on Rare Diseases (ES)
- Centro de Investigación Biomédica en Red (ES)
- European Molecular Biology Laboratory (DE)
- Murdoch Children's Research Institute (AU)
- Monash University (AU)
- Victoria University (AU)
- University of Castilla-La Mancha (ES)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1038/s41467-025-66625-8
- Citations
- 1
- Primary Topic
- Adipose Tissue and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 1.16