Mitochondrial membrane potential and ATP production in primary disorders of ATP synthase.
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 DeltaPsi(m) at state 4 is normal, but ADP-induced discharge of DeltaPsi(m) is impaired and ATP synthesis at state 3-ADP is decreased. Increased DeltaPsi(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 DeltaPsi(m) in primary ATPase disorders could increase mitochondrial production of reactive oxygen species and decrease energy provision.
Vojtísková
Alena
A
Institute of Physiology and Centre for Integrated Genomics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Jesina
Pavel
P
Kalous
Martin
M
Kaplanová
Vilma
V
Houstek
Josef
J
Tesarová
Markéta
M
Fornůsková
Daniela
D
Zeman
Jirí
J
Dubot
Audrey
A
Godinot
Catherine
C