Bipolar disorder is a biphasic
state of energy dysregulation as circadian rithms. Phasic nature of
mitochondria to produce ATP may be crucial to the switching of affective states
in bipolar disorder. Allostatic load of oxidative stress and mitochondrial gene variations have a detrimental effect on mitochondrial function in bipolar patients. Functional polymorphism in the mitochondrial DNA with functional
effects was seen in some regions of brain.
Mitochondrial calcium stimulated
oxidative phosphorylation. Increased levels of calcium increase the activity of
pyruvate dehydrogenase (PDH) leading to increased rate of ATP synthesis in
mitochondria independent of mitochondrial membrane potential. Calcium binds directly to cytochrome C oxidase that acts as the rate limiting enzyme in the mitochondrial electron transported chain, and relieves this inhibition
effectively bypassing feedback mechanism, allowing increased ATP production
even in the presence of high ATP concentration.