| Autor: |
Gundersen AE; Department of Exercise and Health Sciences, University of Massachusetts Boston, Boston, MA 02125, USA., Kugler BA; Department of Exercise and Health Sciences, University of Massachusetts Boston, Boston, MA 02125, USA., McDonald PM; Department of Biology, University of Massachusetts Boston, Boston, MA 02125, USA., Veraksa A; Department of Biology, University of Massachusetts Boston, Boston, MA 02125, USA., Houmard JA; Human Performance Laboratory, East Carolina University, Greenville, NC 27858, USA.; Department of Kinesiology, East Carolina University, Greenville, NC 27858, USA.; East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC 27858, USA., Zou K; Department of Exercise and Health Sciences, University of Massachusetts Boston, Boston, MA 02125, USA. |
| Abstrakt: |
Healthy mitochondrial networks are maintained via balanced integration of mitochondrial quality control processes (biogenesis, fusion, fission, and mitophagy). The purpose of this study was to investigate the effects of severe obesity and type 2 diabetes (T2D) on mitochondrial network morphology and expression of proteins regulating mitochondrial quality control processes in cultured human myotubes. Primary human skeletal muscle cells were isolated from biopsies from lean, severely obese nondiabetic individuals and severely obese type 2 diabetic individuals ( n = 8-9/group) and were differentiated to myotubes. Mitochondrial network morphology was determined in live cells via confocal microscopy and protein markers of mitochondrial quality control were measured by immunoblotting. Myotubes from severely obese nondiabetic and type 2 diabetic humans exhibited fragmented mitochondrial networks ( P < 0.05). Mitochondrial fission protein Drp1 (Ser 616 ) phosphorylation was higher in myotubes from severely obese nondiabetic humans when compared with the lean controls ( P < 0.05), while mitophagy protein Parkin expression was lower in myotubes from severely obese individuals with T2D in comparison to the other groups ( P < 0.05). These data suggest that regulatory proteins in mitochondrial quality control processes, specifically mitochondrial fission protein Drp1 (Ser 616 ) phosphorylation and mitophagy protein Parkin, are intrinsically dysregulated at cellular level in skeletal muscle from severely obese nondiabetic and type 2 diabetic humans, respectively. These differentially expressed mitochondrial quality control proteins may play a role in mitochondrial fragmentation evident in skeletal muscle from severely obese and type 2 diabetic humans. Novelty Mitochondrial network morphology and mitochondrial quality control proteins are intrinsically dysregulated in skeletal muscle cells from severely obese humans with or without T2D. |
