Poster Presentation 47th Lorne Genome Conference 2026

Subcellular proteomic networks underlying acute and chronic exercise responses in human skeletal muscle (133321)

Elizabeth Reisman 1 2 , Dale Taylor 3 , Dingyi Yu 4 , Nikeisha J Caruana 5 , Cheng Huang 6 , David J Bishop 3 , John A Hawley 1 , Nolan J Hoffman 1
  1. Mary MacKillop Institute for Health Research , Australian Catholic University, Melbourne, Vic, Australia
  2. Australian Regenerative Medicine Institute , Monash University, Clayton, Vic, Australia
  3. Institute for Health and Sport, Victoria University, Melbourne, Vic, Australia
  4. Mass Spectrometry Facility, St Vincents Institute of Medical Research, Fitzroy , Vic, Australia
  5. Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Vic, Australia
  6. RNA Mass Spectrometry Platform, Monash University, Clayton, Vic, Australia

INTRODUCTION: Mitochondria serve as critical signalling hubs, integrating and relaying intracellular information to facilitate skeletal muscle adaptations to exercise. Despite known roles of mitochondrial (MITO) protein signalling and translocation between other organelles (i.e., the nucleus and cytosol), major knowledge gaps remain in our understanding of the complex muscle subcellular protein networks underlying acute responses to exercise and exercise training.

METHODS: Muscle biopsies (n=197) were collected from 40 untrained adults (20 women, 20 men; 26.5 ± 5.9 y, VO₂max 31.1 ± 5.6 mL/min/kg) before, during, immediately after, and 3 h post–high-intensity interval exercise (HIIE), and after 8 wk of HIIE training (4 sessions/wk). Subcellular fractionation (MITO, nuclear (NUC), cytosolic (CYTO)) and global mass spectrometry proteomics were used to quantify changes in protein abundance and potential translocation.

RESULTS: Proteomic analysis of 591 total muscle subcellular fractions revealed dynamic exercise-induced changes in MITO, NUC, and CYTO proteins. In the MITO fraction, 1440 proteins (~50% of annotated MITO proteins) were quantified, with 102, 604, and 376 significantly regulated at mid, post, and 3 h post-exercise, and 611 after training (adj. p<0.05). Acute exercise downregulated MITO ribosomal and fission/fusion proteins while upregulating reactive oxygen species–related proteins, whereas training induced broad MITO upregulation consistent with citrate synthase activity and TEM markers of biogenesis. In the NUC fraction, 491 proteins were significantly altered (216 up, 275 down), including those linked to ribonucleotide processes. No sex differences were observed in response to HIIE and 8-wk training.

DISCUSSION & CONCLUSION: These subcellular proteomic datasets represent one of the most extensive human muscle proteome analyses to date. The data highlight a lack of sex-specific differences, robust training-induced mitochondrial biogenesis, and novel pathways of mitochondrial translation and dynamics that warrant further study.