Abstract
We have previously established that 24 h of environmental hyperthermia causes oxidative stress and have implicated mitochondria as likely contributors to this process. Given this, we hypothesized that heat stress would lead to increased autophagy/mitophagy and a reduction in mitochondrial content. To address this hypothesis pigs were housed in thermoneutral (TN; 20°C) or heat stress (35°C) conditions for 1‐ (HS1) or 3‐ (HS3) days and the red and white portions of the semitendinosus collected. We did not detect differences in glycolytic muscle. Counter to our hypothesis, upstream activation of autophagy was largely similar between groups as were markers of autophagosome nucleation and elongation. LC3A/B‐I increased 1.6‐fold in HS1 and HS3 compared to TN (P < 0.05), LC3A/B‐II was increased 4.1‐fold in HS1 and 4.8‐fold in HS3 relative to TN, (P < 0.05) and the LC3A/B‐II/I ratio was increased 3‐fold in HS1 and HS3 compared to TN suggesting an accumulation of autophagosomes. p62 was dramatically increased in HS1 and HS3 compared to TN. Heat stress decreased mitophagy markers PINK1 7.0‐fold in HS1 (P < 0.05) and numerically by 2.4‐fold in HS3 compared to TN and BNIP3L/NIX by 2.5‐fold (P < 0.05) in HS1 and HS3. Markers of mitochondrial content were largely increased without activation of PGC‐1α signaling. In total, these data suggest heat‐stress‐mediated suppression of activation of autophagy and autophagosomal degradation, which may enable the persistence of damaged mitochondria in muscle cells and promote a dysfunctional intracellular environment.
Highlights
Every homeothermic organism has a set temperature range, known as a thermoneutral zone, in which they can adequately maintain an equilibrium of endogenous and exogenous heat production and loss (Swanlund et al 2008)
Autophagy can be initiated via Adenosine Monophosphate Activated Protein Kinase (AMPKa) phosphorylation of Unc51-like kinase 1 (ULK1)
We measured components of the electron transport chain and found a 1.2- and 1.4-fold increase (P = 0.0089) in Complex II Iron-sulfur protein (IP) subunit of succinate dehydrogenase (SDHB) in HS1 and HS3 compared to TN and a 1.3-fold increase (P = 0.0069) in relative abundance of ubiquinol-cytochrome c reductase complex III (UQCRC2) when heat stressed animals were compared to thermoneutral (Fig. 8C and D)
Summary
Every homeothermic organism has a set temperature range, known as a thermoneutral zone, in which they can adequately maintain an equilibrium of endogenous and exogenous heat production and loss (Swanlund et al 2008). Heat stress poses a pressing and urgent threat to human and animal health and wellbeing as well as agricultural economics and food security (Fuquay 1981; MKilbourne 1997; St.-Pierre et al 2003; Haines et al 2006; DeShazer et al 2009; Macpherson 2014).
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