Coenzyme Q-dependent mitochondrial respiratory chain activity in granulosa cells is reduced with aging

Objective To examine coenzyme Q₁₀ (CoQ₁₀)-dependent mitochondrial respiratory chain (MRC) activity in granulosa cells (GC) with aging and examine the effect of in vitro CoQ supplementation. Design Experimental study. Setting Hospital laboratory. Patient(s) Ten younger (<32 years) and 10 older (>39 years) patients undergoing in vitro fertilization (IVF) treatment. Intervention(s) Measurement of succinate-cytochrome c reductase (MRC complex II + III) activity in the presence and absence of CoQ₁ (a soluble CoQ analog). Main Outcome Measure(s) MRC enzymatic activity in human GC via complex II + III measured in GC homogenate by spectrophotometry and compared with CoQ in dependent MRC complex II and citrate synthase (CS). Result(s) Complex II + III activity was 1.9 times higher in young patients compared with older patients (18.3 ± 5.8 and 9.6 ± 3 nmol/min/mg, respectively) whereas II and CS were not statistically significantly different. Increased II + III activity in the presence CoQ₁ was observed in both groups but was statistically significantly higher in the older patients, reaching similar levels. Compared with baseline (II + III + Q/II + III), the increase was 2.47 times higher in older patients compared with young patients (6.5 ± 2.0 and 2.62 ± 0.83, respectively). Conclusion(s) Coenzyme Q₁₀-dependent MRC activity in GC reduces with aging. This reduction is diminished upon in vitro CoQ₁ supplementation, indicating that CoQ₁₀ deficit is the underlying cause for the mitochondrial dysfunction. The results show that functional CoQ₁₀ status can be assessed by measuring complex II + III activity in GC and might provide a useful monitoring tool for future clinical studies of oral CoQ₁₀ supplementation to older patients undergoing IVF treatment.