Abstract
Purpose
Mitochondrial dynamics are regulated by the differing molecular pathways variously governing biogenesis, fission, fusion, and mitophagy. Adaptations in mitochondrial morphology are central in driving the improvements in mitochondrial bioenergetics following exercise training. However, there is a limited understanding of mitochondrial dynamics in response to inactivity.
Methods
Skeletal muscle biopsies were obtained from middle-aged males (n = 24, 49.4 ± 3.2 years) who underwent sequential 14-day interventions of unilateral leg immobilisation, ambulatory recovery, and resistance training. We quantified vastus lateralis gene and protein expression of key proteins involved in mitochondrial biogenesis, fusion, fission, and turnover in at baseline and following each intervention.
Results
PGC1α mRNA decreased 40% following the immobilisation period, and was accompanied by a 56% reduction in MTFP1 mRNA, a factor involved in mitochondrial fission. Subtle mRNA decreases were also observed in TFAM (17%), DRP1 (15%), with contrasting increases in BNIP3L and PRKN following immobilisation. These changes in gene expression were not accompanied by changes in respective protein expression. Instead, we observed subtle decreases in NRF1 and MFN1 protein expression. Ambulatory recovery restored mRNA and protein expression to pre-intervention levels of all altered components, except for BNIP3L. Resistance training restored BNIP3L mRNA to pre-intervention levels, and further increased mRNA expression of OPA-1, MFN2, MTFP1, and PINK1 past baseline levels.
Conclusion
In healthy middle-aged males, 2 weeks of immobilisation did not induce dramatic differences in markers of mitochondria fission and autophagy. Restoration of ambulatory physical activity following the immobilisation period restored altered gene expression patterns to pre-intervention levels, with little evidence of further adaptation to resistance exercise training.
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Data availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- AIFM2:
-
Apoptosis-inducing factor 2
- AR:
-
Ambulatory recovery
- BL:
-
Baseline
- DRP1:
-
Dynamin-1-like protein
- Fis1:
-
Mitochondrial fission 1 protein
- IM:
-
Immobilisation
- LC3B:
-
MAP1 light chain 3
- MFF:
-
Mitochondrial fission factor
- MFN1:
-
Mitofusin 1
- MFN2:
-
Mitofusin 2
- MTFP1:
-
Mitochondrial fission process protein 1
- NRF1:
-
Nuclear regulatory factor 1
- NRF2:
-
Nuclear regulatory factor 2
- OPA1:
-
Optic atrophy 1
- PINK1:
-
PTEN-induced putative kinase 1
- PGC1α:
-
Peroxisome proliferator-activated receptor γ coactivator-1α
- ROS:
-
Reactive oxygen species
- RT:
-
Resistance training
- TFAM:
-
Mitochondrial transcription factor A
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Acknowledgements
The authors acknowledge the volunteers who so willingly contributed to this clinical experimental study. We also thank Aaron Fanning (Fonterra) and Professor Sally Poppitt for their contribution to the New Zealand Primary Growth Partnership (PGP) post-farm gate research program.
Funding
The overall project was funded by the New Zealand Ministry for Primary Industries (MPI) and Fonterra Co-operative Group Ltd through the Primary Growth Partnership (PGP) post-farm gate program, with additional analytical funding from AgResearch Limited through the Strategic Science Investment Fund (Contract Nos. A19079 and A21246: Nutritional strategies for an ageing population). CAP was supported by Ph.D. scholarships from AgResearch Limited and the Agnes Paykel trust.
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Conceived and designed the experiments: CAP, CJM, and DC-S; performed the experiments: CAP, NZ, BRD, RFD, VCF, and CJM; analysed data: CAP and CJM; drafted the manuscript: CAP; wrote the paper: CAP. Critically evaluated the paper: CAP, CPH, AJR, VCF, CJM, and DC-S. All authors edited and revised manuscript and approved the final version of the manuscript.
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Pileggi, C.A., Hedges, C.P., D’Souza, R.F. et al. Minimal adaptation of the molecular regulators of mitochondrial dynamics in response to unilateral limb immobilisation and retraining in middle-aged men. Eur J Appl Physiol 123, 249–260 (2023). https://doi.org/10.1007/s00421-022-05107-x
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DOI: https://doi.org/10.1007/s00421-022-05107-x