Abstract

Research in α-actinin-3 knockout mice suggests a novel role for α-actinin-3 as a mediator of cell signalling. We took advantage of naturally-occurring human "knockouts" (lacking α-actinin-3 protein) to investigate the consequences of α-actinin-3 deficiency on exercise-induced changes in mitochondrial-related genes and proteins, as well as endurance training adaptations. At baseline, we observed a compensatory increase of α-actinin-2 protein in ACTN3 XX (α-actinin-3 deficient; n = 18) vs ACTN3 RR (expressing α-actinin-3; n = 19) participants but no differences between genotypes for markers of aerobic fitness or mitochondrial content and function. There was a main effect of genotype, without an interaction, for RCAN1-4 protein content (a marker of calcineurin activity). However, there was no effect of genotype on exercise-induced expression of genes associated with mitochondrial biogenesis, nor post-training physiological changes. In contrast to results in mice, loss of α-actinin-3 is not associated with higher baseline endurance-related phenotypes, or greater adaptations to endurance exercise training in humans.

RAS ID

31235

Document Type

Journal Article

Date of Publication

9-3-2019

ISSN

2045-2322

Volume

9

Issue

1

PubMed ID

31481717

School

School of Medical and Health Sciences

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

Publisher

Springer

Comments

Papadimitriou, I. D., Eynon, N., Yan, X., Munson, F., Jacques, M., Kuang, J., ... Bishop, D. J. (2019). A “human knockout” model to investigate the influence of the α-actinin-3 protein on exercise-induced mitochondrial adaptations. Scientific Reports, 9, Article 12688. Available here

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Link to publisher version (DOI)

10.1038/s41598-019-49042-y