The Unfolded Protein Response in Skeletal Muscle Adaptations to Exercise

Abstract

The unfolded protein responses of both the mitochondria (UPRmt) and the endoplasmic reticulum (UPRER) are important in maintaining cellular homeostasis during stimulus‐induced increases in protein synthesis. Exercise is a well‐established trigger for the synthesis of mitochondrial proteins via organelle biogenesis, regulated by the transcriptional coactivator PGC‐1a. However, little work has focused on the role that the UPRmt and the UPRER play in exercise‐induced adaptations. To investigate this, we subjected rats to 3 hrs of contractile activity (CCA) for 1, 2, 3, 5 or 7 days, followed by 3 hrs recovery, and examined the gene expression responses involved in early‐onset adaptations to exercise. PGC‐1a mRNA expression increased 12‐fold as early as 1 day of CCA, while the ER chaperone BIP increased in mRNA by 2‐4‐fold between 1‐7 days. Likewise, CHOP expression was elevated 2‐3‐fold throughout 1‐7 days of CCA, while XBP1 mRNA displayed a 47% elevation after 2 days of CCA, but decreased by 26% at 7 days. Expression of upstream UPRmt sensors (LonP, ERa and SirT3) remained unchanged over 7 days of CCA, but the mRNAs encoding the mitochondrial chaperones CPN10, mtHSP70 and HSP60 were elevated by 40‐100% between 2‐7 days of CCA. These changes preceded increases in mitochondrial content and marker proteins such as NQO1. Thus, these findings indicate a potential role of the UPRmt and the UPRER in early exercise‐induced mitochondrial adaptations in skeletal muscle. Supported by NSERC.