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


METHODS
This was a prospective controlled study conducted in an academic medical center.


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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Victor
Victor M
VM
University Hospital Doctor Peset Foundation, Avda Gaspar Aguilar 90, 46017 Valencia, Spain. vmviktor@gmail.com
Rocha
Milagros
M
Bañuls
Celia
C
Sanchez-Serrano
Maria
M
Sola
Eva
E
Gomez
Marcelino
M
Hernandez-Mijares
Antonio
A
D042967:Electron Transport Complex I / Q000502:physiology*; D005260:Female; D005978:Glutathione / Q000032:analysis; D006801:Humans; D007333:Insulin Resistance; D007962:Leukocytes / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D010101:Oxygen Consumption; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D042967:Electron Transport Complex I; D005978:Glutathione