Estrogen and Mitochondria: A New Paradigm for Vascular Protection?

Schematic representation of mitochondrial respiratory chain. The OXPHOS system within the inner mitochondrial membrane is composed of five enzyme complexes. Reoxidation of reducing equivalents such as NADH (reduced nicotinamide adenine nucleotide) or FADH₂ (reduced flavin adenine nucleotide) is coupled to the generation of an electrochemical gradient across the inner mitochondrial membrane. Mitochondrial superoxide is converted to H₂O₂ by Mn superoxide dismutase (MnSOD), and the resulting H₂O₂ is reduced to water by glutathione peroxidase-1 (GPx1). However, H₂O₂, in the presence of reduced transition metals (Fenton reaction), is converted to the highly reactive hydroxyl radical (OH^•). Fe-S centers of enzymes in the tricarboxylic acid cycle and the electron transport chain are major targets of ROS reactivity.