The role of mitochondrial aconitate (ACO2) in human sperm motility

Tang, Min; Liu, Bianjiang; Wang, Shangqian; Xu, Yang; Han, Peng; Li, Peng-Chao; Wang, Zengjun; Song, Ninghong; Zhang, Wei; Chen, Yin

doi:10.3109/19396368.2014.915360

Cited by 23 publications

(13 citation statements)

References 28 publications

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“…YBX1, which is also known as Y-box transcription factor, is involved in spermatogenesis [15,16]. Mitochondrial ACO2 and AK1 are required for sperm motility [13,17]. Consistent with the proteomic 2; Supplementary Table 1), the upregulation of YBX1 and downregulation of ACO2 and AK1 in sperm from the ICSI group were experimentally validated (Fig.…”

Section: Differentially Expressed Proteins Identified In the Sperm Of Infertile Males Who Received Icsisupporting

confidence: 52%

“…Based on the abovementioned results and previous studies [13][14][15][16], we selected three significantly differentially expressed proteins, including ACO2, AK1, and YBX1, for further validation. These proteins are essential for sperm motility and spermatogenesis.…”

Section: Differentially Expressed Proteins Identified In the Sperm Of Infertile Males Who Received Icsimentioning

confidence: 99%

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Proteomic Profile of Sperm in Infertile Males Reveals Changes in Metabolic Pathways

et al. 2021

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The objective of the present study was to investigate the differences in the proteomic profiles of sperm from infertile males with severe oligoasthenoteratozoospermia requiring intracytoplasmic sperm injection (ICSI) and normal control sperm from fertile males. Isobaric tag for relative and absolute quantitation labeling and liquid chromatography–tandem mass spectrometry was performed for identifying proteins in the sperm of infertile and fertile males. Differentially expressed proteins were analyzed via the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases through the Database for Annotation, Visualization, and Integrated Discovery, and protein–protein networks were produced using the Search Tool for Retrieval of Interacting Genes. Immunofluorescence and western blotting verified the differential expression of Y-box-binding protein 1(YBX1), adenylate kinase 1 (AK1), and aconitase 2, mitochondrial (ACO2) proteins. Altogether, 3444 proteins were identified in the sperm of infertile and fertile males, and 938 were differentially expressed between the two groups. Pairwise comparisons revealed that 226 and 712 proteins were significantly upregulated and downregulated in infertile males, respectively. These proteins were significantly enriched in metabolic pathways as per KEGG enrichment analysis. YBX1 expression was upregulated in the sperm heads of patients requiring ICSI treatment, whereas AK1 and ACO2, which are critical enzymes involved in energy metabolism, were downregulated in the sperm tails of the same patients. This result indicates that metabolism may have a crucial role in maintaining normal sperm function. Overall, our results provide insights that will further help in investigating the pathogenic mechanisms of infertility and possible therapeutic strategies.

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Section: Differentially Expressed Proteins Identified In the Sperm Of Infertile Males Who Received Icsisupporting

confidence: 52%

Section: Differentially Expressed Proteins Identified In the Sperm Of Infertile Males Who Received Icsimentioning

confidence: 99%

Proteomic Profile of Sperm in Infertile Males Reveals Changes in Metabolic Pathways

et al. 2021

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“…ACO2 is an enzyme involved in the second step of the TCA cycle, that catalyzes the interconversion of citrate to isocitrate. Little is known about the role and mechanism of ACO2 in asthenozoospermia, although immunoblotting experiments demonstrated that the level of ACO2 protein in the asthenozoospermic samples was significantly decreased in comparison to normal fertile men [21]. It is interesting to underline that mitochondrial aconitase activity could be considered a functional indicator of mitochondrial levels of reactive oxygen species (ROS), because the iron-sulfur core of this enzyme is oxidized by superoxide anions, reducing its activity [22].…”

Section: Discussionmentioning

confidence: 99%

Comparative Proteomic Analysis of Proteins Involved in Bioenergetics Pathways Associated with Human Sperm Motility

Moscatelli

Lunetti

Braccia

et al. 2019

IJMS

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Sperm motility is the most important parameter involved in the fertilization process and it is strictly required for reproductive success. Although sperm movements are essential for the physiologic fertilization process, the data, deriving from studies focused on the research of altered cell pathways involved in asthenozoospermia, offer only limited information about the molecular mechanism underlying sperm motility. The aim of this study was to identify proteins involved in human sperm motility deficiency by using label-free mass-spectrometry liquid chromatography (LC−MS/MS). For this purpose, we selected sperm samples with three different classes of progressive motility: low, medium (asthenozoospermic samples) and high (normozoospermic samples). We found that several differential expressed proteins in asthenozoospermic samples were related to energetic metabolism, suggesting an interesting link between bioenergetics pathways and the regulation of sperm motility, necessary for the flagellum movement. Therefore, our results provide strong evidence that mass spectrometry-based proteomics represents an integrated approach to detect novel biochemical markers of sperm motility and quality with diagnostic relevance for male infertility and unravel the molecular etiology of idiopathic cases.

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“…Our results showed that ACO2 protein increased by 60% in ISCA1 knockout embryos (Figure A,C), unlike the observed decrease in Fe/S transfer protein. ACO2 is central to carbohydrate and energy metabolism and is associated with multiple metabolic pathways and pathologic conditions such as Huntington's Disease, hypoxia, and reactive oxygen species (ROS) and energy metabolism defects . ACO2 production could be regulated by cell energy metabolism and the observed increase in ACO2 activity might counteract cell energy metabolism defects .…”

Section: Discussionmentioning

confidence: 99%

“…ACO2 is central to carbohydrate and energy metabolism and is associated with multiple metabolic pathways and pathologic conditions such as Huntington's Disease, hypoxia, and reactive oxygen species (ROS) and energy metabolism defects . ACO2 production could be regulated by cell energy metabolism and the observed increase in ACO2 activity might counteract cell energy metabolism defects . We speculated that the ISCA1 knockout resulted in damage to the mitochondrial respiratory chain complex I via a decrease in NDUFA9 protein, leading to defective energy metabolism.…”

Section: Discussionmentioning

confidence: 99%

Knockout of ISCA1 causes early embryonic death in rats

Yang

Zhang

et al. 2019

Anim Models and Exp Med

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Background Iron‐sulfur cluster assembly 1 ( ISCA 1) is an iron‐sulfur (Fe/S) carrier protein that accepts Fe/S from a scaffold protein and transfers it to target proteins including the mitochondrial Fe/S containing proteins. ISCA 1 is also the newly identified causal gene for multiple mitochondrial dysfunctions syndrome ( MMDS ). However, our knowledge about the physiological function of ISCA 1 in vivo is currently limited. In this study, we generated an ISCA 1 knockout rat line and analyzed the embryo development. Methods ISCA 1 knockout rats were generated by replacing the exon1 of ISCA 1 gene with the mC herry‐Cre fusion gene using CRISPR ‐Cas9 technology. The ISCA 1 expression pattern was analyzed by fluorescence imaging using ISCA 1 promotor driven Cre and mC herry expression. The embryonic morphology was examinated by microscope and mitochondrial proteins were tested by Western blot. Results An ISCA 1 knockout rat line was obtained, which expressed mC herry‐Cre fusion protein. Both of the fluorescence images from mC herry and Cre induced mC herry in a reporter rat strain, showing that ISCA 1 expressed in most of the tissues in rats. The ISCA 1 knockout resulted in abnormal development at 8.5 days, with a significant decrease of NDUFA 9 protein and an increase of aconitase 2 ( ACO 2) in rat embryos. Conclusion Deletion of ISCA 1 induced early death in rats. ISCA 1 affected the expression of key proteins in the mitochondrial respiratory chain complex, suggesting that ISCA 1 has an important influence on the respiratory complex and energy metabolism.

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The role of mitochondrial aconitate (ACO2) in human sperm motility

Cited by 23 publications

References 28 publications

Proteomic Profile of Sperm in Infertile Males Reveals Changes in Metabolic Pathways

Proteomic Profile of Sperm in Infertile Males Reveals Changes in Metabolic Pathways

Comparative Proteomic Analysis of Proteins Involved in Bioenergetics Pathways Associated with Human Sperm Motility

Knockout of ISCA1 causes early embryonic death in rats

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