Profiling Mitochondrial Quality Control in Human Myotubes Derived from Severely Obese Non‐diabetic and Type 2 Diabetic Patients

Abstract

Mitochondrial networks are maintained via integration of mitochondrial quality control processes, including biogenesis, fusion/fission dynamics and mitophagy. There is evidence to suggest that mitochondrial quality control plays a critical role in the regulation of mitochondrial function and glucose metabolism in skeletal muscle, and disruptions of these processes accompany the presence of skeletal muscle insulin resistance and type 2 diabetes (T2D). However, whether disruptions of mitochondrial quality control processes are retained at the muscle cell level is largely unknown. The purpose of this study was to determine whether the expression of proteins involved in mitochondrial quality control processes were dysregulated in primary human myotubes derived from type 2 diabetic patients. Primary human skeletal muscle cells were isolated from muscle biopsies obtained from eight severely obese, non‐diabetic subjects (BMI = 52.4 kg/m2, fasting glucose = 98.9 mg/dl) and eight severely obese, type 2 diabetics (BMI = 49 kg/m2, fasting glucose 132.3 mg/dl), and were differentiated to myotubes. On day 7 of differentiation, myotubes were harvested for immunoblot analysis to assess the expression of proteins involved in each of the four mitochondrial quality control processes. Mitochondrial fusion protein expression (Optic Atrophy Protein 1 (Opa1) and Mitofusin 1 (Mfn1)) were significantly lower in myotubes derived from type 2 diabetic patients in comparison to the BMI‐matched, non‐diabetic subjects (0.038 ± 0.003 vs. 0.024 ± 0.002 and 0.440 ± 0.042 vs. 0.320 ± 0.038, respectively, P < 0.05). In addition, expression of the mitophagic protein Parkin was significantly lower in primary myotubes derived from type 2 diabetic patients (0.0028 ± 0.0003 vs. 0.0018 ± 0.0002, P < 0.05). No significant differences were found in expression of other fusion or mitophagy proteins (Mitofusin 2 (Mfn2), or PTEN‐Induced Putative Kinase 1 (PINK1)), or proteins related to mitochondrial fission (dynamin related protein 1 (Drp1) and mitochondrial fission 1 protein (Fis1)), and biogenesis (PGC‐1α). These data suggest that mitochondrial quality control is dysregulated in primary myotubes derived from type 2 diabetic patients in a manner that favors fission over fusion.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.