Research Paper Volume 11, Issue 11 pp 3750—3767

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

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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.