This Article Full Text Full Text (PDF) Supplemental Data Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Google Scholar Articles by Victor, V. M. Articles by Hernandez-Mijares, A. PubMed PubMed Citation Articles by Victor, V. M. Articles by Hernandez-Mijares, A. Related Collections Female Endocrinology

Mitochondrial Complex I Impairment in Leukocytes from Polycystic Ovary Syndrome Patients with Insulin Resistance

University Hospital Doctor Peset Foundation (V.M.V., M.R., A.H.-M.), Avda Gaspar Aguilar 90, 46017 Valencia, Spain; University Hospital Doctor Peset (V.M.V., M.R., C.B., M.S.-S., E.S., M.G., A.H.-M.), Endocrinology Service, Avda Gaspar Aguilar 90, 46017 Valencia, Spain; Department of Physiology (V.M.V.), University of Valencia, 46010 Valencia, Spain; Department of Medicine (A.H.-M.), University of Valencia, 46010 Valencia, Spain; and Research Group Centro de Investigación Biomédica en Red (CIBER) CB/06/02/0045 Actions in Epidemiology and Public Health (C.B., A.H.-M.), 46017 Valencia, Spain

Address all correspondence and requests for reprints to: Victor M. Victor and A. Hernandez-Mijares, University Hospital Doctor Peset Foundation, Avda Gaspar Aguilar 90, 46017 Valencia, Spain. E-mail: vmviktor{at}gmail.com and hernandez_antmij{at}gva.es.

Context: Insulin resistance is a feature of polycystic ovary syndrome (PCOS) and is related to mitochondrial function.

Objective: Our objective was to assess mitochondrial function by evaluating mitochondrial oxygen (O₂) consumption, reactive oxygen species (ROS) production, levels of glutathione (GSH), the oxidized glutathione/GSH ratio, TNF levels, and membrane potential. Additionally, we have evaluated mitochondrial complex I as a target of the oxidative stress responsible for PCOS in polymorphonuclear cells.

Design and Setting: This was a prospective controlled study conducted in an academic medical center.

Patients: The study population consisted of 20 lean reproductive-age women with PCOS and 20 body composition-matched controls.

Main Outcome Measures: We evaluated mitochondrial O₂ consumption using the Clark-type O₂ electrode; levels of ROS, GSH, and membrane potential by means of fluorescence microscopy; TNF levels by ELISA; and complex I activity by spectrophotometric assay.

Results: An impairment in mitochondrial function was observed in PCOS patients, evident by a decrease in mitochondrial O₂ consumption; an increase in ROS production, oxidized glutathione/GSH ratio, and TNF levels; a drop in GSH levels; and an undermining of membrane potential. Furthermore, an impairment of mitochondrial complex I was identified.

Conclusion: 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.