PARK7 protein translocating into spermatozoa mitochondria in Chinese asthenozoospermia

Abstract

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.

Downregulation of DJ-1 Fails to Protect Mitochondrial Complex I Subunit NDUFS3 in the Testes and Contributes to the Asthenozoospermia

“…Our previous studies confirmed the significant reduction in DJ-1 in the sperm of patients with AS [ 19 , 20 ]. NDUFS3 was identified as a single band of approximately ~30 kDa by Western blot ( Figure 1(a) ).…”

“…DJ-1 is expressed after second spermatocytes appear during spermatogenesis and is ultimately mainly located in the sperm head, suggesting an important function for DJ-1 in spermatogenesis [ 17 , 18 ]. Downregulation of DJ-1 was found in ejaculated sperm from Chinese patients with AS, and DJ-1 was shown to translocate into sperm mitochondria during oxidative stress to maintain mitochondrial structure [ 19 , 20 ].…”

MiR‐4485‐3p expression reduced in spermatozoa of men with idiopathic asthenozoospermia

“…Klinefelter, Laskey, Ferrell, Suarez, and Roberts (), for the first time, discovered the relationship between PARK7 and male infertility in Rat (Klinefelter et al, ). The mRNA and protein expression of this gene reduced in AZS men in comparison with normal men (An et al, ), and this decline associated with reactive oxygen species (ROS) increase and damage to mitochondria that lead to sperm motility reduction (Sun et al, ). Sevaral SNPs in the promotor of PARK7 gene have been shown to be associated with asthenozoospermia (Jahantigh, Hosseinzadeh Colagar, & Salimi, ).…”

DJ1 expression downregulates in neuroblastoma cells (SK-N-MC) chronically exposed to HIV-1 and cocaine

“…Thus, the key factor that regulates all these functions will be of prime importance to understand this highly complicated disease pathology. In order to address this issue, we have investigated DJ1, a protein that is abundant in the brain and also a key regulator of DA transmission and reactive oxygen species (ROS) balance ( Blesa and Przedborski, 2014 ; Lopert and Patel, 2014 ; Sun et al, 2014 ).…”

“…DJ-1 (PARK7) is a neuroprotective protein that protects cells from oxidative stress ( Lopert and Patel, 2014 ; Sun et al, 2014 ). Initially, DJ-1 gene was linked to autosomal recessive early-onset of PD.…”