Figure 6.

Model of the role that AT1 and AT2 receptors play in modulating oxidative phosphorylation in brain mitochondria. Activation of AT1 receptors in mitochondria regulates superoxide production, via Nox4, and increases respiration. Mitochondrial AT2 receptors are much more abundant and induce, via nitric oxide, a decrease in mitochondrial respiration, modulating oxidative phosphorylation without significant alteration in mitochondrial membrane potential, which indicates that the bioenergetic properties of the mitochondria are not affected. Mitochondrial AT2 receptor expression increased after treatment of cells with oxidative stress (OS) inducers (such as low doses of MPP⁺) and decreased with aging. Mitochondrial AT1 expression increased with aging and after treatment of cells with antioxidants (such as N-acetyl-cysteine, NAC). At mitochondrial level, AT2 receptors may act as respiratory modulators and counteract low levels of OS, which may be particularly important in cells with an increase in levels of OS such as dopaminergic neurons. Aging induces altered expression of mitochondrial AT1 and AT2 receptors that may induce mitochondrial dysfunction, the main risk factor for neurodegeneration