Abid 2020 FASEB J

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Abid H, Ryan ZC, Delmotte P, Sieck GC, Lanza IR (2020) Extramyocellular interleukin-6 influences skeletal muscle mitochondrial physiology through canonical JAK/STAT signaling pathways. FASEB J 34:14458-72.

» PMID: 32885495 Open Access

Abid Hinnah, Ryan Zachary C, Delmotte Philippe, Sieck Gary C, Lanza Ian R (2020) FASEB J

Abstract: Interleukin-6 (IL-6) is a pleiotropic cytokine that has been shown to be produced acutely by skeletal muscle in response to exercise, yet chronically elevated with obesity and aging. The mechanisms by which IL-6 influences skeletal muscle mitochondria acutely and chronically are unclear. To better understand the influence of extramyocellular IL-6 on skeletal muscle mitochondrial physiology, we treated differentiated myotubes with exogenous IL-6 to evaluate the dose- and duration-dependent effects of IL-6 on salient aspects of mitochondrial biology and the role of canonical IL-6 signaling in muscle cells. Acute exposure of myotubes to IL-6 increased the mitochondrial reactive oxygen species (mtROS) production and oxygen consumption rates (JO2) in a manner that was dependent on activation of the JAK/STAT pathway. Furthermore, STAT3 activation by IL-6 was partly attenuated by MitoQ, a mitochondrial-targeted antioxidant, suggesting that mtROS potentiates STAT3 signaling in skeletal muscle in response to IL-6 exposure. In concert with effects on mitochondrial physiology, acute IL-6 exposure induced several mitochondrial adaptations, consistent with the stress-induced mitochondrial hyperfusion. Exposure of myotubes to chronically elevated IL-6 further increased mtROS with eventual loss of respiratory capacity. These data provide new evidence supporting the interplay between cytokine signaling and mitochondrial physiology in skeletal muscle.

Keywords: STAT3, Interleukin-6, Mitochondria, Reactive oxygen species, Skeletal muscle Bioblast editor: Plangger M O2k-Network Lab: US MN Rochester Nair KS


Labels: MiParea: Respiration, Pharmacology;toxicology 

Stress:Oxidative stress;RONS  Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Intact cells 


Coupling state: LEAK, OXPHOS  Pathway: N, S, NS  HRR: Oxygraph-2k, O2k-Fluorometer 

2020-09, AmR