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choline dehydrogenase interacts with SQSTM1 to activate mitophagy and promote coelomocyte survival in Apostichopus japonicus following Vibrio splendidus infection

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动物学研究(英文) 2023年第5期44卷 905-918页

作者： Lian-Lian Sun Ying-Fen Dai Mei-Xiang You Cheng-Hua Li State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products Ningbo UniversityNingboZhejiang 315211China Laboratory for Marine Fisheries Science and Food Production Processes Qingdao National Laboratory for Marine Science and TechnologyQingdaoShandong 266071China

Previous studies have shown that Vibrio splendidus infection causes mitochondrial damage in Apostichopus japonicus coelomocytes,leading to the production of excessive reactive oxygen species(ROS)and irreversible apoptotic cell *** evidence suggests that mitochondrial autophagy(mitophagy)is the most effective method for eliminating damaged mitochondria and ROS,with choline dehydrogenase(CHDH)identified as a novel mitophagy receptor that can recognize non-ubiquitin damage signals and microtubule-associated protein 1 light chain 3(LC3)in ***,the functional role of CHDH in invertebrates is largely *** this study,we observed a significant increase in the mRNA and protein expression levels of *** CHDH(AjCHDH)in response to *** infection and lipopolysaccharide(LPS)challenge,consistent with changes in mitophagy under the same ***,AjCHDH was localized to the mitochondria rather than the cytosol following *** ***,AjCHDH knockdown using si RNA transfection significantly reduced mitophagy levels,as observed through transmission electron microscopy and confocal *** investigation into the molecular mechanisms underlying CHDH-regulated mitophagy showed that AjCHDH lacked an LC3-interacting region(LIR)for direct binding to LC3 but possessed a FB1 structural domain that binds to *** interaction between AjCHDH and SQSTM1 was further confirmed by immunoprecipitation ***,laser confocal microscopy indicated that SQSTM1 and LC3 were recruited by AjCHDH in coelomocytes and HEK293T *** contrast,AjCHDH interference hindered SQSTM1 and LC3 recruitment to the mitochondria,a critical step in damaged mitochondrial ***,AjCHDH interference led to a significant increase in both mitochondrial and intracellular ROS,followed by increased apoptosis and decreased coelomocyte ***,these findings indicate that AjCHDH-mediated mitophagy plays a

关键词： choline dehydrogenase Mitophagy SQSTM1 Microtubule-associated protein 1 light chain 3 Apostichopus japonicus

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Phosphatidylethanolamine N-methyltransferase and choline dehydrogenase gene polymorphisms are associated with human sperm concentration

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Asian Journal of Andrology 2012年第5期14卷 778-783页

作者： Leandros Lazaros Nectaria Xita Elissavet Hatzi Apostolos Kaponis Georgios Makrydimas Atsushi Takenaka Nikolaos Sofikitis Theodoros Stefos Konstantinos Zikopoulos Ioannis Georgiou Genetics and IVF Unit Department of Obstetrics and Gynecology Medical School University of Ioannina Ioannina 45110 Greece Department of Endocrinology Medica School University of Ioannina Ioannina 45110 Greece Department of Urology Tottori University Faculty of Medicine Totteri 683-8504 Japan Department of Urology Medical School University of Ioannina Ioannina 45110 Greece

choline is a crucial factor in the regulation of sperm membrane structure and fluidity, and this nutrient plays an important role in the maturation and fertilizing capacity of spermatozoa. Transcripts of phosphatidylethanolamine N-methyltransferase （PEMT） and choline dehydrogenase （CHDH）, two basic enzymes of choline metabolism, have been observed in the human testis, demonstrating their gene expression in this tissue. In the present study, we explored the contribution of the PEMTand CHDHgene variants to sperm parameters. Two hundred oligospermic and 250 normozoospermic men were recruited. DNA was extracted from the spermatozoa, and the PEMT -774G〉C and CHDH ＋432G〉T polymorphisms were genotyped. The genotype distribution of the PEMT-774G〉C polymorphism did not differ between oligospermic and normozoospermic men. In contrast, in the case of the CHDH ＋432G〉T polymorphism, oligospermic men presented the CHDH432GIG genotype more frequently than normozoospermic men （62% vs. 42%, P〈0.001）. The PEMT774GIG genotype was associated with a higher sperm concentration compared to the PEMT774GIC and 774C/C genotypes in oligospermic men （12.5±5.6× 10^6 spermatozoa m1-1 vs. 8.3±5.2×10^6 spermatozoa m1-1, P〈0.002） and normozoospermic men （81.5±55.6×10^6 vs. 68.1±44.5×10^6 spermatozoa m1-1, P〈0.006）. In addition, the CHDH432G/G genotype was associated with higher sperm concentration compared to CHDH432G.T and 432T/T genotypes in oligospermic （11.8±5.1×10^6 vs. 7.8±5.3×10^6 spermatozoa m1-1, P〈0.003） and normozoospermic men （98.6±62.2×10^6 vs. 58.8±＋33.6×10^6 spermatozoa m1-1, P〉0.001）. In our series, the PEMT-774G〈C and CHDH ＋432G〈T polymorphisms were associated with sperm concentration. This finding suggests a possible influence of these genes on sperm quality.

关键词： choline dehydrogenase male infertility phosphatidylethanolamine N-methyltransferase phospholipids spermconcentration

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