Skeletal muscle mitochondrial function and exercise capacity are not impaired in mice with knockout of STAT3

Abstract

Signal transducer and activator of transcription 3 (STAT3) was recently found to be localized to mitochondria in a number of tissues and cell types, where it modulates oxidative phosphorylation via interactions with the electron transport proteins, complex I and complex II. Skeletal muscle is densely populated with mitochondria although whether STAT3 contributes to skeletal muscle oxidative capacity is unknown. In the present study, we sought to elucidate the contribution of STAT3 to mitochondrial and skeletal muscle function by studying mice with muscle-specific knockout of STAT3 (mKO). First, we developed a novel flow cytometry-based approach to confirm that STAT3 is present in skeletal muscle mitochondria. However, contrary to findings in other tissue types, complex I and complex II activity and maximal mitochondrial respiratory capacity in skeletal muscle were comparable between mKO mice and floxed/wild-type littermates. Moreover, there were no genotype differences in endurance exercise performance, skeletal muscle force-generating capacity, or the adaptive response of skeletal muscle to voluntary wheel running. Collectively, although we confirm the presence of STAT3 in skeletal muscle mitochondria, our data establish that STAT3 is dispensable for mitochondrial and physiological function in skeletal muscle. NEW & NOTEWORTHY Whether signal transducer and activator of transcription 3 (STAT3) can regulate the activity of complex I and II of the electron transport chain and mitochondrial oxidative capacity in skeletal muscle, as it can in other tissues, is unknown. By using a mouse model lacking STAT3 in muscle, we demonstrate that skeletal muscle mitochondrial and physiological function, both in vivo and ex vivo, is not impacted by the loss of STAT3.

Protective Effect of Delta-Like 1 Homolog Against Muscular Atrophy in a Mouse Model

“…Sixth, changes in mitochondrial function by DLK1 treatment was not investigated. As intact mitochondrial function is an important determinant to prevent muscle atrophy [ 49 ], further experiments such as high-resolution respirometry to measure mitochondrial function [ 50 , 51 ], are needed to support the benefit of DLK1 on sarcopenia.…”

Targeting the JAK2/STAT3 Pathway—Can We Compare It to the Two Faces of the God Janus?

“…Satellite skeletal muscle cells maturing in a state of cachexia are characterized by Pax7 expression, corresponding with their proliferation, with no expression of myogenin, which proves impaired regeneration ability [43]. Thus, it is suspected that STAT3 promotes the expansion of the pool of satellite cells and plays a negative role in the differentiation and repair processes of skeletal muscles [44]. On the other hand, some of the most recent reports on the role of STAT3 in the functioning of skeletal muscle mitochondria are surprising and confirm the need for further research on STAT3 in skeletal muscles.…”