Prohibitin involvement in the generation of mitochondrial superoxide at complex I in human sperm

• Published in: Journal of cellular and molecular medicine Vol. 21; no. 1; pp. 121 - 129
• Main Authors: Chai, Ran‐Ran, Chen, Guo‐Wu, Shi, Hui‐Juan, O, Wai‐Sum, Martin‐DeLeon, Patricia A., Chen, Hong
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.01.2017; John Wiley and Sons Inc
• Subjects: Adult; Catalytic subunits; Electron transport; Electron transport chain; Electron Transport Complex I - metabolism; Fertility; Flow cytometry; human sperm; Humans; In vitro fertilization; Lipid peroxidation; Lipid Peroxidation - drug effects; Lipids; Male; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Membrane proteins; Metabolism; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; mitochondrial complex I; mitochondrial ROS; Motility; NADH-ubiquinone oxidoreductase; Original; Oxidative stress; Peroxidation; Physiology; Prohibitin; Reactive Oxygen Species - metabolism; Repressor Proteins - pharmacology; Sperm; Sperm Count - methods; sperm motility; Sperm Motility - drug effects; Spermatozoa - drug effects; Spermatozoa - metabolism; Superoxide; Superoxides - metabolism; United States > US; human sperm; sperm motility; mitochondrial complex I; prohibitin; mitochondrial ROS
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.12945

Prohibitin (PHB), a major mitochondrial membrane protein, has been shown earlier in our laboratoryto regulate sperm motility via an alteration in mitochondrial membrane potential (MMP) in infertile men with poor sperm quality. To test if PHB expression is associated with sperm mitochondrial superoxide (mROS) levels, here we examined sperm mROS levels, high MMP and lipid peroxidation in infertile men with poor sperm motility (asthenospermia, A) and/or low sperm concentrations (oligoasthenospermia, OA). The diaphorase‐type activity of sperm mitochondrial complex I (MCI) and PHB expression were also determined. We demonstrate that mROS and lipid peroxidation levels are significantly higher in sperm from A and OA subjects than in normospermic subjects, whereas high MMP and PHB expression are significantly lower. A positive correlation between mROS and lipid peroxidation and a negative correlation of mROS with PHB expression, high MMP, and sperm motility were found in these subjects. The finding of similar diaphorase‐type activity levels of sperm MCI in the three groups studied suggests that the catalytic subunits of MCI in the matrix arm may produce mROS on its own. There may be a dysfunction of electron transport at MCI associated with decreased expression of PHB in sperm with poor quality. We conclude that mROS level is increased and associated with decreased PHB expression, and it may regulate sperm motility via increases in low MMP and lipid peroxidation. This is the first report on the involvement of PHB in human sperm motility loss associated with increased generation of mROS at MCI.