Heat stress causes dysfunctional autophagy in oxidative skeletal muscle. Issue 12 (23rd June 2017)

• Record Type: Journal Article
• Authors: Brownstein, Alexandra J.; Ganesan, Shanthi; Summers, Corey M.; Pearce, Sarah; Hale, Benjamin J.; Ross, Jason W.; Gabler, Nicholas; Seibert, Jacob T.; Rhoads, Robert P.; Baumgard, Lance H.; Selsby, Joshua T.
• Is Part Of: Physiological reports. Volume 5:Issue 12(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-06-23
• Subjects: Heat stroke -- hyperthermia -- mitochondria -- mitophagy -- oxidative stress; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.13317
• Languages: English
• ISSNs: 2051-817X

Abstract

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‐1 α 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. Abstract : Long‐term exposure to hyperthermic conditions negatively impacts human and animal health and agricultural profitability, however, the development of therapeutic interventions has been delayed due to a poor understanding of underlying cellular dysfunctions. Here, we demonstrate that heat stress disrupts autophagy in oxidative muscle, whereas glycolytic muscle appears to be largely resistant to hyperthermic muscle injury.