Περίληψη:
Mitochondrial membrane potential (MMP) is the most reliable indicator of
mitochondrial function. The MMP value range of -136 to -140 mV has been
considered optimal for maximum ATP production for all living organisms.
Even small changes from the above range result in a large fall in ATP
production and a large increase in ROS production. The resulting
bioenergetic deregulation is considered as the causative agent for
numerous major human diseases. Normalization of MMP value improves
mitochondrial function and gives excellent therapeutic results. In order
for a systematic effective treatment of these diseases to be developed,
a detailed knowledge of the mechanism of MMP production is absolutely
necessary. However, despite the long-standing research efforts, a
concrete mechanism for MMP production has not been found yet.
The present paper proposes a novel mechanism of MMP production based on
new considerations underlying the function of the two basic players of
MMP production, the electron transport chain (ETC) and the F1F0 ATP
synthase. Under normal conditions, MMP is almost exclusively produced by
the electron flow through ETC complexes I-IV, creating a direct electric
current that stops in subunit II of complex IV and gradually charges
MMP. However, upon ETC dysfunction F1F0 ATP synthase reverses its action
and starts to hydrolyze ATP. ATP hydrolysis further produces electric
energy which is transferred, in the form of a direct electric current,
from F1 to F0 where is used to charge MMP. This new model is expected to
redirect current experimental research on mitochondrial bioenergetics
and indicate new therapeutic schemes for mitochondrial disorders. (C)
2014 Elsevier Ltd. All rights reserved.
Συγγραφείς:
Bagkos, Georgios
Koufopoulos, Kostas
Piperi, Christina
