Voltage-dependent anion channels are a key factor of male fertility

Kwon, Woo-Sung; Park, Yoo-Jin; Elsayed, Mohamed; Pang, Myung-Geol

doi:10.1016/j.fertnstert.2012.09.021

Cited by 89 publications

(101 citation statements)

References 68 publications

(68 reference statements)

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“…VDAC2 probably controls sperm motility by regulating energy metabolism [40]. Kwon et al (2013) demonstrated that blocking the VDAC2 and VDAC3 gene caused significantly decreased sperm motility, acrosome reaction, capacitation, tyrosine phosphorylation, fertilization, and embryo development, suggesting that VDACs are essential for successful reproduction [41]. It seems that, by regulating energy metabolism, VDAC2 has a pivotal role in male fertility and may be a good candidate for diagnosis of sperm dysfunction, and use as a predictor of embryo quality.…”

Section: Discussionmentioning

confidence: 99%

A proteomic analysis on human sperm tail: comparison between normozoospermia and asthenozoospermia

Hashemitabar

Sabbagh

Orazizadeh

et al. 2015

J Assist Reprod Genet

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Purpose Asthenozoospermia is a common cause of human male infertility characterized by reduced sperm motility. The molecular mechanism that impairs sperm motility is not fully understood. This study proposed to identify novel biomarkers by focusing on sperm tail proteomic analysis of asthenozoospermic patients. Methods Sperm were isolated from normozoospermic and asthenozoospermic semen samples. Tail fractions were obtained by sonication followed by Percoll gradient. The proteins were extracted by solubilization and subjected to two-dimensional gel electrophoresis (2-DE); then, the spots were analyzed using Image Master 2D Platinum software. The significantly increased/ decreased amounts of proteins in the two groups were exploited by matrix-assisted laser desorption-ionization time-of-flight/ time-of-flight (MALDI-TOF-TOF) mass spectrometry. Results Three hundred ninety protein spots were detected in both groups. Twenty-one protein spots that had significantly altered amounts (p<0.05) were excised and exploited using MALDI-TOF-TOF mass spectrometry. They led to the identification of the following 14 unique proteins: Tubulin beta 2B; glutathione S-transferase Mu 3; keratin, type II cytoskeletal 1; outer dense fiber protein 2; voltage-dependent anionselective channel protein 2; A-kinase anchor protein 4; cytochrome c oxidase subunit 6B; sperm protein associated with the nucleus on the X chromosome B; phospholipid hydroperoxide glutathione peroxidase-mitochondrial; isoaspartyl peptidase/L-asparaginase; heat shock-related 70 kDa protein 2; stress-70 protein, mitochondrial; glyceraldehyde-3-phosphate dehydrogenase, testis-specific and clusterin. Conclusion Fourteen proteins present in different amounts in asthenozoospermic sperm tail samples were identified, four of which are reported here for the first time. These proteins might be used as markers for the better diagnosis of sperm dysfunctions, targets for male contraceptive development, and to predict embryo quality.

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Section: Discussionmentioning

confidence: 99%

A proteomic analysis on human sperm tail: comparison between normozoospermia and asthenozoospermia

Hashemitabar

Sabbagh

Orazizadeh

et al. 2015

J Assist Reprod Genet

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“…An additional member of the models mass lists is voltage-dependent anion channel 2. This pore-forming protein is involved in the membrane transport of ions and small molecules and has been found in sperm of different species, with relevant roles including functions related with motility, capacitation and fertilization (43). COX4I is the terminal enzyme of the respiratory chain and is necessary for ATP synthesis (44), so lower levels of this protein may be associated with defective sperm functions including motility (45) and other energetic metabolic dependent functions.…”

Section: Fertility Phenotyping Through Sperm Icm-msmentioning

confidence: 99%

Intact Cell MALDI-TOF MS on Sperm: A Molecular Test For Male Fertility Diagnosis

Soler

Labas

Thélie

et al. 2016

Molecular & Cellular Proteomics

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“…VDACs 2 and 3) were novel acetylated proteins in human sperm. In mammals, VDACs are poreforming proteins mainly located in the outer mitochondrial membrane (50); they have already been identified as key determinants of male fertility (51). In addition, human VDAC2 has been found in the acrosomal membrane or plasma membrane of sperm where it mediates Ca 2ϩ transmembrane transport (52).…”

Section: Table I Synthesized Peptides Peptide Libraries and Peptide-mentioning

confidence: 99%

Acetylproteomic Analysis Reveals Functional Implications of Lysine Acetylation in Human Spermatozoa (sperm)

Diao

Wang

et al. 2015

Molecular & Cellular Proteomics

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Male infertility is a medical condition that has been on the rise globally. Lysine acetylation of human sperm, an essential posttranslational modification involved in the etiology of sperm abnormality, is not fully understood. Therefore, we first generated a qualified pan-anti-acetyllysine monoclonal antibody to characterize the global lysine acetylation of uncapacitated normal human sperm with a proteomics approach. With high enrichment ratios that were up to 31%, 973 lysine-acetylated sites that matched to 456 human sperm proteins, including 671 novel lysine acetylation sites and 205 novel lysine-acetylated proteins, were identified. These proteins exhibited conserved motifs XXXKYXXX, XXXKFXXX, and XXXKHXXX, were annotated to function in multiple metabolic processes, and were localized predominantly in the mitochondrion and cytoplasmic fractions. Between the uncapacitated and capacitated sperm, different acetylation profiles in regard to functional proteins involved in sperm capacitation, sperm-egg recognition, sperm-egg plasma fusion, and fertilization were observed, indicating that acetylation of functional proteins may be required during sperm capacitation. Bioinformatics analysis revealed association of acetylated proteins with diseases and drugs. Novel acetylation of voltage-dependent anion channel proteins was also found. With clinical sperm samples, we observed differed lysine acetyltransferases and lysine deacetylases expression between normal sperm and abnormal sperm of asthenospermia or necrospermia. Furthermore, with sperm samples impaired by epigallocatechin gallate to mimic asthenospermia, we observed that inhibition of sperm motility was partly through the blockade of voltage-dependent anion channel 2 Lys-74 acetylation combined with reduced ATP levels and mitochondrial membrane potential. Taken together, we obtained a qualified pananti-acetyllysine monoclonal antibody, analyzed the acetylproteome of uncapacitated human sperm, and revealed associations between functional protein acetylation and sperm functions. Molecular & Cellular

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Voltage-dependent anion channels are a key factor of male fertility

Cited by 89 publications

References 68 publications

A proteomic analysis on human sperm tail: comparison between normozoospermia and asthenozoospermia

A proteomic analysis on human sperm tail: comparison between normozoospermia and asthenozoospermia

Intact Cell MALDI-TOF MS on Sperm: A Molecular Test For Male Fertility Diagnosis

Acetylproteomic Analysis Reveals Functional Implications of Lysine Acetylation in Human Spermatozoa (sperm)

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