Research Paper Volume 11, Issue 11 pp 3750—3767

Mitochondrial and autophagic alterations in skin fibroblasts from Parkinson disease patients with Parkin mutations

Figure 1. Mitochondrial respiratory control ratios in control and PRKN-PD fibroblasts. Illustrative mitochondrial respiration flux profile indicating respiratory control parameters (image obtained from Agilent Seahorse XF) (A), basal respiration (B), ATP-linked respiration (C), maximal respiration (D), spare respiratory capacity (E) and basal/maximal respiratory ratio (F). In glucose, no significant differences were found between PRKN-PD and control fibroblasts in the respiratory control ratios although trends to increased basal and maximal as well as ATP-linked respirations and decreased spare respiratory capacity were observed. In galactose, PRKN-PD fibroblasts exhibited a significant decrease in basal/maximal respiratory ratio compared to the control fibroblasts as well as a downward trend in the basal respiration and ATP-linked respiration. Controls but not PRKN-PD significantly increased oxygen consumption linked to ATP production and the basal/maximal respiratory ratio in galactose compared to glucose. Both, control and PRKN-PD fibroblasts significantly decreased the spare respiratory capacity upon medium change. Each cell line was seeded in triplicate per condition (n=3 for GLC and n=3 for GAL). The results were expressed as means and standard error of the mean (SEM). *= p<0.05. CTL= Control fibroblasts. GAL= 10 mM galactose medium. GLC= 25 mM glucose medium. NS= not significant. OCR= Oxygen consumption rate. PRKN-PD= Parkin-associated PD fibroblasts. Respiratory control ratios were normalized by total protein content and by citrate synthase activity as a marker of mitochondrial content.