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Heat Stress Causes Autophagic Stalling In Oxidative Skeletal Muscle
Author(s) -
Brownstein Alexandra,
Summers Corey,
Ganesan Shanthi,
Hale Benjamin,
Pearce Sarah,
Gabler Nicholas,
Ross Jason W,
Rhoads Robert P.,
Baumgard Lance H.,
Selsby Joshua T.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1290.15
Subject(s) - autophagy , mitophagy , sequestosome 1 , oxidative stress , microbiology and biotechnology , skeletal muscle , mitochondrion , biology , autophagosome , medicine , endocrinology , chemistry , apoptosis , biochemistry
Heat stress (HS) poses a threat to human and animal health and well being, and serves to undermine agricultural economics and food security. Yet, little is known about underlying pathological mechanisms caused by HS, which impedes the development of effective mitigation strategies. To address this critical need we have been working to elucidate HS‐mediated dysfunction in skeletal muscle and have implicated the mitochondria as likely contributors to cellular pathology. Given the possibility of mitochondrial dysfunction we hypothesized that cells would respond to HS by clearing damaged mitochondria via autophagy. To test this hypothesis gilts (female pigs; 35±4 kg; n=5–6/group) were housed in thermoneutral (TN; 20 ± 1°C) or HS (35°C) conditions for one (HS1) or three days (HS3). Relative protein abundance of markers of autophagosome membrane nucleation, Phosphatidylinositide 3‐kinases class III, Beclin‐1, elongation (Autophagy‐related protein 16L1), and maturation of autophagosomes (Microtubule‐associated protein A/B‐light chain 3 II) was increased (p<0.05) following 1 and 3 days of HS. Conversely, sequestosome‐1 (p62), a selective autophagy receptor consumed by autophagy and inversely associated with autophagy flux, was not detected in TN pigs, dramatically increased following 1 day of HS, and decreased by 3.4‐fold (but was still readily detectable) following 3 days of HS compared to 1 day of HS (p<0.05). Gene expression of p62 was similar between groups. In addition, mitophagy marker, BCL2/Adenovirus E1B 19kDa interacting protein 3‐like (Bnip3L) was decreased 2.5‐fold (p<0.05) after 1 and 3 days of HS and PTEN‐induced putative kinase 1 (PINK1) was decreased 7.0‐fold following 1 day of HS (p<0.05) and numerically by 2.4‐fold following 3 days of HS. Together, these data suggest that HS drives autophagy but this process stalls resulting in the accumulation of autophagosomes, suppressed mitophagy, and the preservation of dysfunctional mitochondria Support or Funding Information Supported by USDA grants 2014‐67015‐21627 and 2011‐67003‐30007.