Mitochondrial complex I impairment in leukocytes from polycystic ovary syndrome patients with insulin resistance.

Abstract

Insulin resistance is a feature of polycystic ovary syndrome (PCOS) and is related to mitochondrial function. Our objective was to assess mitochondrial function by evaluating mitochondrial oxygen (O(2)) consumption, reactive oxygen species (ROS) production, levels of glutathione (GSH), the oxidized glutathione/GSH ratio, TNFalpha levels, and membrane potential. Additionally, we have evaluated mitochondrial complex I as a target of the oxidative stress responsible for PCOS in polymorphonuclear cells. This was a prospective controlled study conducted in an academic medical center. The study population consisted of 20 lean reproductive-age women with PCOS and 20 body composition-matched controls. We evaluated mitochondrial O(2) consumption using the Clark-type O(2) electrode; levels of ROS, GSH, and membrane potential by means of fluorescence microscopy; TNFalpha levels by ELISA; and complex I activity by spectrophotometric assay. An impairment in mitochondrial function was observed in PCOS patients, evident by a decrease in mitochondrial O(2) consumption; an increase in ROS production, oxidized glutathione/GSH ratio, and TNFalpha levels; a drop in GSH levels; and an undermining of membrane potential. Furthermore, an impairment of mitochondrial complex I was identified. This study supports the hypothesis of an association between insulin resistance and an impaired mitochondrial oxidative metabolism. We also propose that the oxidative stress responsible for PCOS takes place at complex I. These abnormalities may contribute to the increased risk of type 2 diabetes among women with PCOS.