PARK7 protein translocating into spermatozoa mitochondria in Chinese asthenozoospermia.

PARK7 (DJ1) is a multifunctional oxidative stress response protein that protects cells against reactive oxygen species (ROS) and mitochondrial damage. PARK7 defects are known to cause various physiological dysfunctions, including infertility. Asthenozoospermia (AS), i.e. low-motile spermatozoa in the ejaculate, is a common cause of human male infertility. In this study, we found that downregulation of PARK7 resulted in increased levels of lipid peroxide and ROS, decreased mitochondrial membrane potential, and reduced mitochondrial complex I enzyme activity in the spermatozoa from AS patients. Furthermore, it was observed that PARK7 was translocated into the mitochondria of damaged spermatozoa in AS. Finally, we examined the oxidative state of PARK7 and the results demonstrated the enhancement of oxidation, expressed by increased sulfonic acid residues, the highest form of oxidation, as the sperm motility decreased. Taken together, these results revealed that PARK7 deficiency may increase the oxidative stress damage to spermatozoa. Our present findings open new avenues of therapeutic intervention targeting PARK7 for the treatment of AS.

[1]  N. Tajiri,et al.  Oxygen–Glucose‐Deprived Rat Primary Neural Cells Exhibit DJ‐1 Translocation into Healthy Mitochondria: A Potent Stroke Therapeutic Target , 2013, CNS neuroscience & therapeutics.

[2]  S. Longobardi,et al.  Protective effects of in vitro treatment with zinc, d-aspartate and coenzyme q10 on human sperm motility, lipid peroxidation and DNA fragmentation , 2013, Reproductive Biology and Endocrinology.

[3]  Ji Hoon Park,et al.  DJ-1 Null Dopaminergic Neuronal Cells Exhibit Defects in Mitochondrial Function and Structure: Involvement of Mitochondrial Complex I Assembly , 2012, PloS one.

[4]  X. Pu,et al.  Down-regulation of DJ-1 protein in the ejaculated spermatozoa from Chinese asthenozoospermia patients. , 2011, Fertility and sterility.

[5]  A. Freitas,et al.  Not All Sperm Are Equal: Functional Mitochondria Characterize a Subpopulation of Human Sperm with Better Fertilization Potential , 2011, PloS one.

[6]  A. Lenzi,et al.  Altered ultrastructure of mitochondrial membranes is strongly associated with unexplained asthenozoospermia. , 2011, Fertility and sterility.

[7]  M. Lou,et al.  Glutaredoxin 2 prevents H(2)O(2)-induced cell apoptosis by protecting complex I activity in the mitochondria. , 2010, Biochimica et biophysica acta.

[8]  N. Bonini,et al.  DJ-1 is critical for mitochondrial function and rescues PINK1 loss of function , 2010, Proceedings of the National Academy of Sciences.

[9]  R. Krüger,et al.  Reduced Basal Autophagy and Impaired Mitochondrial Dynamics Due to Loss of Parkinson's Disease-Associated Protein DJ-1 , 2010, PloS one.

[10]  K. Takahashi-Niki,et al.  DJ-1 binds to mitochondrial complex I and maintains its activity. , 2009, Biochemical and biophysical research communications.

[11]  A. Amaral,et al.  Mitochondrial functionality in reproduction: from gonads and gametes to embryos and embryonic stem cells. , 2009, Human reproduction update.

[12]  B. Lin,et al.  Proteomic analysis of seminal plasma from asthenozoospermia patients reveals proteins that affect oxidative stress responses and semen quality. , 2009, Asian journal of andrology.

[13]  Xin Zhao,et al.  Mitochondrial localization of DJ‐1 leads to enhanced neuroprotection , 2009, Journal of neuroscience research.

[14]  R. Aitken,et al.  Significance of mitochondrial reactive oxygen species in the generation of oxidative stress in spermatozoa. , 2008, The Journal of clinical endocrinology and metabolism.

[15]  P. Piomboni,et al.  Oxygen uptake by mitochondria in demembranated human spermatozoa: a reliable tool for the evaluation of sperm respiratory efficiency. , 2008, International journal of andrology.

[16]  A. Agarwal,et al.  REVIEW ARTICLE: Clinical Relevance of Oxidative Stress in Male Factor Infertility: An Update , 2007, American journal of reproductive immunology.

[17]  T. Dawson,et al.  DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase , 2007, Proceedings of the National Academy of Sciences.

[18]  A. Amaral,et al.  The expression of polymerase gamma and mitochondrial transcription factor A and the regulation of mitochondrial DNA content in mature human sperm. , 2007, Human reproduction.

[19]  T. Taira,et al.  Induction of reactive oxygen species by bisphenol A and abrogation of bisphenol A-induced cell injury by DJ-1. , 2005, Toxicological sciences : an official journal of the Society of Toxicology.

[20]  T. Niki,et al.  Reduced anti-oxidative stress activities of DJ-1 mutants found in Parkinson's disease patients. , 2004, Biochemical and biophysical research communications.

[21]  David W. Miller,et al.  The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[22]  Tomoya Kinumi,et al.  Cysteine-106 of DJ-1 is the most sensitive cysteine residue to hydrogen peroxide-mediated oxidation in vivo in human umbilical vein endothelial cells. , 2004, Biochemical and biophysical research communications.

[23]  T. Niki,et al.  DJ‐1 has a role in antioxidative stress to prevent cell death , 2004, EMBO reports.

[24]  H. Ariga,et al.  Down regulation of DJ-1 enhances cell death by oxidative stress, ER stress, and proteasome inhibition. , 2003, Biochemical and biophysical research communications.

[25]  H. Ariga,et al.  Immunocytochemical localization of DJ‐1 in human male reproductive tissue , 2003, Molecular reproduction and development.

[26]  G. Mendeluk,et al.  ASTHENOZOOSPERMIA: ANALYSIS OF A LARGE POPULATION , 2003, Archives of andrology.

[27]  Patrizia Rizzu,et al.  Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism , 2002, Science.

[28]  T. Niki,et al.  DJ-1, a target protein for an endocrine disrupter, participates in the fertilization in mice. , 2002, Biological & pharmaceutical bulletin.

[29]  G. Klinefelter,et al.  Localization of the sperm protein SP22 and inhibition of fertility in vivo and in vitro. , 2002, Journal of andrology.

[30]  A. Mitsumoto,et al.  DJ-1 is an indicator for endogenous reactive oxygen species elicited by endotoxin , 2001, Free radical research.

[31]  A. Iwamatsu,et al.  Oxidized forms of peroxiredoxins and DJ-1 on two-dimensional gels increased in response to sublethal levels of paraquat , 2001, Free radical research.

[32]  E. Ruiz-Pesini,et al.  Seminal quality correlates with mitochondrial functionality. , 2000, Clinica chimica acta; international journal of clinical chemistry.

[33]  M. Leisner,et al.  Ultrastructural pathology of the sperm flagellum: association between flagellar pathology and fertility prognosis in severely asthenozoospermic men. , 1998, Human reproduction.

[34]  E. Ruiz-Pesini,et al.  Correlation of sperm motility with mitochondrial enzymatic activities. , 1998, Clinical chemistry.

[35]  G. Klinefelter,et al.  SP22: a novel fertility protein from a highly conserved gene family. , 1998, Journal of andrology.

[36]  K. Strupat,et al.  Shedding of a rat epididymal sperm protein associated with infertility induced by ornidazole and alpha-chlorohydrin. , 1998, Biology of reproduction.

[37]  J. Laskey,et al.  Discriminant analysis indicates a single sperm protein (SP22) is predictive of fertility following exposure to epididymal toxicants. , 1997, Journal of andrology.

[38]  T. Taira,et al.  DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras. , 1997, Biochemical and biophysical research communications.

[39]  R. Willson,et al.  Stimulation of microsomal lipid peroxidation by iron and cysteine. Characterization and the role of free radicals. , 1983, The Biochemical journal.

[40]  Banajit Bastia,et al.  Role of Oxidative Stress and Antioxidants in Male Infertility , 2015 .

[41]  S. Iguchi-Ariga,et al.  DJ-1-Mediated protective effect of protocatechuic aldehyde against oxidative stress in SH-SY5Y cells. , 2011, Journal of pharmacological sciences.

[42]  T. Niki,et al.  Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities , 2006, Cell Death and Differentiation.

[43]  T. Ryder,et al.  Asthenozoospermia and the human sperm mid-piece. , 1995, Human reproduction.