Papadimitriou 2019 Sci Rep
|Papadimitriou ID, Eynon N, Yan X, Munson F, Jacques M, Kuang J, Voisin S, North KN, Bishop DJ (2019) A "human knockout" model to investigate the influence of the α-actinin-3 protein on exercise-induced mitochondrial adaptations. Sci Rep 9:12688.|
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.
Labels: MiParea: Respiration, Genetic knockout;overexpression, Exercise physiology;nutrition;life style
Organism: Human Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS, ET Pathway: N, S, NS, ROX HRR: Oxygraph-2k