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

Ran‐Ran Chai,Guo‐Wu Chen,Patricia A Martin‐Deleon,Hui‐Juan Shi,Wai‐Sum O,Hong Chen

doi:10.1111/jcmm.12945

Abstract

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.

Highlights

Reactive oxygen species (ROS), such as superoxide anions, hydroxyl radicals and H2O2, can be produced during cellular metabolism and are maintained at physiological levels by endogenous enzymatic and non-enzymatic antioxidants
Mitochondrial dysfunction is significantly correlated with human sperm motility loss in asthenospermic or oligoasthenospermic subjects
Correlation analysis showed that mitochondrial high membrane potential was positively correlated with the total sperm motility (Pearson r = 0.4386, P = 0.0006; see Fig. 2C) and progressive motility (Pearson r = 0.4278, P = 0.0008; see Fig. 2D), but negatively correlated with mitochondrial ROS (Pearson r = À0.8445, P < 0.0001; see Fig. 2B)

Summary

Introduction

Reactive oxygen species (ROS), such as superoxide anions, hydroxyl radicals and H2O2, can be produced during cellular metabolism and are maintained at physiological levels by endogenous enzymatic and non-enzymatic antioxidants. For example in somatic cells, the major source of ROS generation is electron leakage from mitochondrial electron transport chain (ETC) during cellular respiration [1]. Once the fine balance controlled by antioxidant factors within the inter-membrane space and mitochondrial matrix [2] is lost, mitochondrial ROS production may generate oxidative stress that has been implicated in numerous pathological conditions, including Alzheimer’s [3] and Parkinson’s disease [4]. Current evidence supports the generation of ROS by sperm mitochondria in rabbits [5, 6], rats [7] and human [8], but the factors responsible for excessive mitochondrial free radical generation remains unidentified.

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