Role of gp130 in basal and exercise-trained skeletal muscle mitochondrial quality control

Dennis K. Fix, Justin P. Hardee, Song Gao, Brandon N. VanderVeen, Kandy T. Velázquez, James Carson

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The IL-6 cytokine family activates intracellular signaling pathways through glycoprotein-130 (gp130), and this signaling has established regulatory roles in muscle glucose metabolism and proteostasis. Although the IL-6 family has been implicated as myokines regulating the muscles’ metabolic response to exercise, gp130’s role in mitochondrial quality control involving fission, fusion, mitophagy, and biogenesis is not well understood. Therefore, we examined gp130’s role in basal and exercise-trained muscle mitochondrial quality control. Muscles from C57BL/6, skeletal muscle-specific gp130 knockout (KO) mice, and C2C12 myotubes, were examined. KO did not alter treadmill run-to-fatigue or indices of mitochondrial content [cytochrome-c oxidase (COX) activity] or biogenesis (AMPK, peroxisome proliferator-activated receptor- coactivator-1, mitochondrial transcription factor A, and COX IV). KO increased mitochondrial fission 1 protein (FIS-1) while suppressing mitofusin-1 (MFN-1), which was recapitulated in myotubes after gp130 knockdown. KO induced ubiquitin-binding protein p62, Parkin, and ubiquitin in isolated mitochondria from gastrocnemius muscles. Knockdown of gp130 in myotubes suppressed STAT3 and induced accumulation of microtubule-associated protein-1 light chain 3B (LC3)-II relative to LC3-I. Suppression of myotube STAT3 did not alter FIS-1 or MFN-1. Exercise training increased muscle gp130 and suppressed STAT3. KO did not alter the exercise-training induction of COX activity, biogenesis, FIS-1, or Beclin-1. KO increased MFN-1 and suppressed 4-hydroxynonenal after exercise training. These findings suggest a role for gp130 in the modulation of mitochondrial dynamics and autophagic processes. NEW & NOTEWORTHY Although the IL-6 family of cytokines has been implicated in the regulation of skeletal muscle protein turnover and metabolism, less is understood about its role in mitochondrial quality control. We examined the glycoprotein-130 receptor in the regulation of skeletal muscle mitochondria quality control in the basal and exercise-trained states. We report that the muscle glycopro-tein-130 receptor modulates basal mitochondrial dynamics and autophagic processes and is not necessary for exercise-training mitochondrial adaptations to quality control.

Original languageEnglish (US)
Pages (from-to)1456-1470
Number of pages15
JournalJournal of applied physiology
Volume124
Issue number6
DOIs
StatePublished - Jun 1 2018

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Quality Control
Glycoproteins
Skeletal Muscle
Skeletal Muscle Fibers
Mitochondrial Dynamics
Muscles
Exercise
Interleukin-6
Oxidoreductases
Mitochondrial Degradation
Muscle Mitochondrion
Cytokines
Light
Peroxisome Proliferator-Activated Receptors
AMP-Activated Protein Kinases
Microtubule-Associated Proteins
Muscle Proteins
Electron Transport Complex IV
Ubiquitin
Knockout Mice

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

Role of gp130 in basal and exercise-trained skeletal muscle mitochondrial quality control. / Fix, Dennis K.; Hardee, Justin P.; Gao, Song; VanderVeen, Brandon N.; Velázquez, Kandy T.; Carson, James.

In: Journal of applied physiology, Vol. 124, No. 6, 01.06.2018, p. 1456-1470.

Research output: Contribution to journalArticle

Fix, Dennis K. ; Hardee, Justin P. ; Gao, Song ; VanderVeen, Brandon N. ; Velázquez, Kandy T. ; Carson, James. / Role of gp130 in basal and exercise-trained skeletal muscle mitochondrial quality control. In: Journal of applied physiology. 2018 ; Vol. 124, No. 6. pp. 1456-1470.
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