Important role of mitochondria and the effect of mood stabilizers on mitochondrial function.

摘要

Mitochondria primarily serve as source of cellular energy throughthe Krebs cycle and β-oxidation to generate substrates foroxidative phosphorylation. Redox reactions are used to transferelectrons through a gradient to their final acceptor, oxygen, andto pump hydrogen protons into the intermembrane space. Then,ATP synthase uses the electrochemical gradient to generateadenosine triphosphate (ATP). During these processes, reactiveoxygen species (ROS) are generated. ROS are highly reactivemolecules with important physiological functions in cellularsignaling. Mitochondria play a crucial role in intracellular calciumhomeostasis and serve as transient calcium stores. High levels ofboth, ROS and free cytosolic calcium, can damage mitochondrialand cellular structures and trigger apoptosis. Impairedmitochondrial function has been described in many psychiatricdiseases, including mood disorders, in terms of loweredmitochondrial membrane potential, suppressed ATP formation,imbalanced Ca2+ levels and increased ROS levels. In vitro modelshave indicated that mood stabilizers affect mitochondrialrespiratory chain complexes, ROS production, ATP formation,Ca2+ buffering and the antioxidant system. Most studies supportthe hypothesis that mitochondrial dysfunction is a primaryfeature of mood disorders. The precise mechanism of action ofmood stabilizers remains unknown, but new mitochondrialtargets have been proposed for use as mood stabilizers andmitochondrial biomarkers in the evaluation of therapyeffectiveness.