Mitochondrial Membrane Potential and ATP Production in Primary Disorders of ATP Synthase

Abstract

Studies of fibroblasts with primary defects in mitochondrial ATP synthase (ATPase) due to heteroplasmic mtDNA mutations in the ATP6 gene, affecting protonophoric function or synthesis of subunit a, show that at high mutation loads, mitochondrial membrane potential ΔΨ_m at state 4 is normal, but ADP-induced discharge of ΔΨ_m is impaired and ATP synthesis at state 3-ADP is decreased. Increased ΔΨ_m and low ATP synthesis is also found when the ATPase content is diminished by altered biogenesis of the enzyme complex. Irrespective of the different pathogenic mechanisms, elevated ΔΨ_m in primary ATPase disorders could increase mitochondrial production of reactive oxygen species and decrease energy provision.

Keywords: :

• ATP Synthase
• ATP6
• Flow Cytometry
• Membrane Potential
• Mitochondrial diseases
• mtDNA