title: High-fat diet-induced mitochondrial biogenesis is regulated by mitochondrial-derived reactive oxygen species activation of CaMKII.
abstract: Calcium/calmodulin-dependent protein kinase (CaMK) activation induces mitochondrial biogenesis in response to increasing cytosolic calcium concentrations. Calcium leak from the ryanodine receptor (RyR) is regulated by reactive oxygen species (ROS), which is increased with high-fat feeding. We examined whether ROS-induced CaMKII-mediated signaling induced skeletal muscle mitochondrial biogenesis in selected models of lipid oversupply. In obese Zucker rats and high-fat-fed rodents, in which muscle mitochondrial content was upregulated, CaMKII phosphorylation was increased independent of changes in calcium uptake because sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) protein expression or activity was not altered, implicating altered sarcoplasmic reticulum (SR) calcium leak in the activation of CaMKII. In support of this, we found that high-fat feeding increased mitochondrial ROS emission and S-nitrosylation of the RyR, whereas hydrogen peroxide induced SR calcium leak from the RyR and activation of CaMKII. Moreover, administration of a mitochondrial-specific antioxidant, SkQ, prevented high-fat diet-induced phosphorylation of CaMKII and the induction of mitochondrial biogenesis. Altogether, these data suggest that increased mitochondrial ROS emission is required for the induction of SR calcium leak, activation of CaMKII, and induction of mitochondrial biogenesis in response to excess lipid availability.
authors: Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
authors: Swati S
authors: SS
authors: Jain
authors: Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
authors: Sabina
authors: S
authors: Paglialunga
authors: Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.
authors: Chris
authors: C
authors: Vigna
authors: Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
authors: Alison
authors: A
authors: Ludzki
authors: Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
authors: Eric A
authors: EA
authors: Herbst
authors: Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
authors: James S
authors: JS
authors: Lally
authors: Department of Human Biology, Maastricht University, Maastricht, the Netherlands.
authors: Patrick
authors: P
authors: Schrauwen
authors: Department of Human Biology, Maastricht University, Maastricht, the Netherlands.
authors: Joris
authors: J
authors: Hoeks
authors: Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.
authors: A Russ
authors: AR
authors: Tupling
authors: Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
authors: Arend
authors: A
authors: Bonen
authors: Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada ghollowa@uoguelph.ca.
authors: Graham P
authors: GP
authors: Holloway
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D020013:Calcium Signaling / Q000502:physiology; D002135:Calcium-Binding Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D059305:Diet, High-Fat; D004789:Enzyme Activation; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D032342:Muscle Cells / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D011924:Rats, Zucker; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D001786:Blood Glucose; D002135:Calcium-Binding Proteins; D017382:Reactive Oxygen Species; D019831:Sodium-Calcium Exchanger; D006861:Hydrogen Peroxide; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2