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Loss of mammalian glutaminase orthologs impairs sperm function in Caenorhabditis elegans

The decline in sperm function is a major cause of human male infertility. Glutaminase, a mitochondrial enzyme that catalyzes the hydrolysis of glutamine to generate glutamate, takes part in many diverse biological processes such as neurotransmission, metabolism, and cellular senescence. Here we repo...

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Detalles Bibliográficos
Autores principales: Liang, Qifei, Yang, Haiyan, Zhang, Zhifei, Zheng, Jialin C., Qin, Zhao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9982271/
https://www.ncbi.nlm.nih.gov/pubmed/36876125
http://dx.doi.org/10.1016/j.isci.2023.106206
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author Liang, Qifei
Yang, Haiyan
Zhang, Zhifei
Zheng, Jialin C.
Qin, Zhao
author_facet Liang, Qifei
Yang, Haiyan
Zhang, Zhifei
Zheng, Jialin C.
Qin, Zhao
author_sort Liang, Qifei
collection PubMed
description The decline in sperm function is a major cause of human male infertility. Glutaminase, a mitochondrial enzyme that catalyzes the hydrolysis of glutamine to generate glutamate, takes part in many diverse biological processes such as neurotransmission, metabolism, and cellular senescence. Here we report the role of glutaminase in regulating sperm function. By generating a triple mutant that harbors a loss-of-function allele for each of all three mammalian glutaminase orthologs, we found that glutaminase gene activity is required for optimal Caenorhabditis elegans sperm function. Tissue-specific gene manipulations showed that germline glutaminase activity plays an important role. Moreover, transcriptional profiling and antioxidant treatment suggested that glutaminase promotes sperm function by maintaining cellular redox homeostasis. As maintaining a low level of ROS is crucial to human sperm function, it is very likely that glutaminase plays a similar role in humans and therefore can be a potential target for treating human male infertility.
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spelling pubmed-99822712023-03-04 Loss of mammalian glutaminase orthologs impairs sperm function in Caenorhabditis elegans Liang, Qifei Yang, Haiyan Zhang, Zhifei Zheng, Jialin C. Qin, Zhao iScience Article The decline in sperm function is a major cause of human male infertility. Glutaminase, a mitochondrial enzyme that catalyzes the hydrolysis of glutamine to generate glutamate, takes part in many diverse biological processes such as neurotransmission, metabolism, and cellular senescence. Here we report the role of glutaminase in regulating sperm function. By generating a triple mutant that harbors a loss-of-function allele for each of all three mammalian glutaminase orthologs, we found that glutaminase gene activity is required for optimal Caenorhabditis elegans sperm function. Tissue-specific gene manipulations showed that germline glutaminase activity plays an important role. Moreover, transcriptional profiling and antioxidant treatment suggested that glutaminase promotes sperm function by maintaining cellular redox homeostasis. As maintaining a low level of ROS is crucial to human sperm function, it is very likely that glutaminase plays a similar role in humans and therefore can be a potential target for treating human male infertility. Elsevier 2023-02-15 /pmc/articles/PMC9982271/ /pubmed/36876125 http://dx.doi.org/10.1016/j.isci.2023.106206 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Liang, Qifei
Yang, Haiyan
Zhang, Zhifei
Zheng, Jialin C.
Qin, Zhao
Loss of mammalian glutaminase orthologs impairs sperm function in Caenorhabditis elegans
title Loss of mammalian glutaminase orthologs impairs sperm function in Caenorhabditis elegans
title_full Loss of mammalian glutaminase orthologs impairs sperm function in Caenorhabditis elegans
title_fullStr Loss of mammalian glutaminase orthologs impairs sperm function in Caenorhabditis elegans
title_full_unstemmed Loss of mammalian glutaminase orthologs impairs sperm function in Caenorhabditis elegans
title_short Loss of mammalian glutaminase orthologs impairs sperm function in Caenorhabditis elegans
title_sort loss of mammalian glutaminase orthologs impairs sperm function in caenorhabditis elegans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9982271/
https://www.ncbi.nlm.nih.gov/pubmed/36876125
http://dx.doi.org/10.1016/j.isci.2023.106206
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