Interaction of Cytochrome C Oxidase with Steroid Hormones

• Main Authors: Ilya P. Oleynikov, Natalia V. Azarkina, Tatiana V. Vygodina, Alexander A. Konstantinov
• Format: Article
• Language: English
• Published: MDPI AG 2020-09-01
• Series: Cells
• Subjects: cytochrome oxidase; steroid hormones; regulation
• Online Access: https://www.mdpi.com/2073-4409/9/10/2211

Estradiol, testosterone and other steroid hormones inhibit cytochrome <i>c</i> oxidase (CcO) purified from bovine heart. The inhibition is strongly dependent on concentration of dodecyl-maltoside (DM) in the assay. The plots of K_i vs [DM] are linear for both estradiol and testosterone which may indicate an 1:1 stoichiometry competition between the hormones and the detergent. Binding of estradiol, but not of testosterone, brings about spectral shift of the oxidized CcO consistent with an effect on heme <i>a</i>₃³⁺. We presume that the hormones bind to CcO at the bile acid binding site described by Ferguson-Miller and collaborators. Estradiol is shown to inhibit intraprotein electron transfer between hemes <i>a</i> and <i>a</i>₃_. Notably, neither estradiol nor testosterone suppresses the peroxidase activity of CcO. Such a specific mode of action indicates that inhibition of CcO activity by the hormones is associated with impairing proton transfer via the K-proton channel.