Canonical Mitochondrial Biogenesis And Mitochondrial Translation Following Multiple Bouts Of Disuse

Abstract

Muscular disuse affects a great number of people with sedentary lifestyles and/or chronic disease. Disuse has been shown to cause severe muscular atrophy and to disrupt mitochondrial quality. The mitochondrial genome encodes 13 proteins critical to oxidative phosphorylation for which the mitochondria contains its own equipment for mRNA translation. PURPOSE:To examine if disuse affects canonical mitochondrial biogenesis and mitochondrial mRNA translation, and if resistance exercise following bouts of unloading can promote biogenesis. METHODS:Sprague-Dawley rats were subjected to chronic disuse atrophy by hindlimb unloading (28-d, 1HU) followed by ambulatory recovery (56-d) with (1HU+EX) and without (1HU+REC) resistance exercise. To mimic repeated bouts of disuse animals were subjected to a second bout of HU (28-d, 2HU) and allowed ambulatory recovery with (2HU+EX) or without (2HU+REC) resistance exercise. Control (CON) animals were allowed normal cage activity throughout. Samples were analyzed for Pgc-1α, Tfam, Nrf2, Pparα, Tufm, and Taco1 mRNA content by real time RT-PCR. To test if disuse impacted mitochondrial biogenesis regulators a T-Test was performed between CON and 1HU groups, to test impact of reloading and exercise data were analyzed by one-way ANOVA across all groups with α set at P<0.05. RESULTS:Pgc-1α content was 59% and Nrf2 75% lower following disuse (1HU) compared to CON. 1HU+Ex exhibited 280% greater Pparα content and 278% greater Tfam content (p=0.013) compared to CON. Pgc-1α (80%), Pparα (208%), and Tfam (195%)contents were significantly greater with exercise recovery (1HU+Ex) than without (1HU+Rec). Nrf2 was 61% lower with 2HU. Tufm (-73%) and Taco1(-78%) contents were both significantly lower in 1HU. 1HU+Exshowed significantly greater Tufm (123%) and Taco1 (149%) contents when compared to CON. CONCLUSIONS: A single bout of disuse decreases the expression of canonical biogenesis markers and mitochondrial mRNA translation targets. 1HU+Ex promotes mitochondrial biogenesis more than 1HU+Rec. Multiple bouts of disuse decreases the expression of Nrf2.