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SLC22A14 is a mitochondrial riboflavin transporter required for sperm oxidative phosphorylation and male fertility
Ablation of Slc22a14 causes male infertility in mice, but the underlying mechanisms remain unknown. Here, we show that SLC22A14 is a riboflavin transporter localized at the inner mitochondrial membrane of the spermatozoa mid-piece and show by genetic, biochemical, multi-omic, and nutritional evidenc...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065176/ https://www.ncbi.nlm.nih.gov/pubmed/33882315 http://dx.doi.org/10.1016/j.celrep.2021.109025 |
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author | Kuang, Wenhua Zhang, Jie Lan, Zhou Deepak, R.N.V. Krishna Liu, Chao Ma, Zhilong Cheng, Lili Zhao, Xinbin Meng, Xianbin Wang, Weihua Wang, Xueying Xu, Lina Jiao, Yupei Luo, Qi Meng, Ziyi Kee, Kehkooi Liu, Xiaohui Deng, Haiteng Li, Wei Fan, Hao Chen, Ligong |
author_facet | Kuang, Wenhua Zhang, Jie Lan, Zhou Deepak, R.N.V. Krishna Liu, Chao Ma, Zhilong Cheng, Lili Zhao, Xinbin Meng, Xianbin Wang, Weihua Wang, Xueying Xu, Lina Jiao, Yupei Luo, Qi Meng, Ziyi Kee, Kehkooi Liu, Xiaohui Deng, Haiteng Li, Wei Fan, Hao Chen, Ligong |
author_sort | Kuang, Wenhua |
collection | PubMed |
description | Ablation of Slc22a14 causes male infertility in mice, but the underlying mechanisms remain unknown. Here, we show that SLC22A14 is a riboflavin transporter localized at the inner mitochondrial membrane of the spermatozoa mid-piece and show by genetic, biochemical, multi-omic, and nutritional evidence that riboflavin transport deficiency suppresses the oxidative phosphorylation and reprograms spermatozoa energy metabolism by disrupting flavoenzyme functions. Specifically, we find that fatty acid β-oxidation (FAO) is defective with significantly reduced levels of acyl-carnitines and metabolites from the TCA cycle (the citric acid cycle) but accumulated triglycerides and free fatty acids in Slc22a14 knockout spermatozoa. We demonstrate that Slc22a14-mediated FAO is essential for spermatozoa energy generation and motility. Furthermore, sperm from wild-type mice treated with a riboflavin-deficient diet mimics those in Slc22a14 knockout mice, confirming that an altered riboflavin level causes spermatozoa morphological and bioenergetic defects. Beyond substantially advancing our understanding of spermatozoa energy metabolism, our study provides an attractive target for the development of male contraceptives. |
format | Online Article Text |
id | pubmed-8065176 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-80651762021-04-27 SLC22A14 is a mitochondrial riboflavin transporter required for sperm oxidative phosphorylation and male fertility Kuang, Wenhua Zhang, Jie Lan, Zhou Deepak, R.N.V. Krishna Liu, Chao Ma, Zhilong Cheng, Lili Zhao, Xinbin Meng, Xianbin Wang, Weihua Wang, Xueying Xu, Lina Jiao, Yupei Luo, Qi Meng, Ziyi Kee, Kehkooi Liu, Xiaohui Deng, Haiteng Li, Wei Fan, Hao Chen, Ligong Cell Rep Article Ablation of Slc22a14 causes male infertility in mice, but the underlying mechanisms remain unknown. Here, we show that SLC22A14 is a riboflavin transporter localized at the inner mitochondrial membrane of the spermatozoa mid-piece and show by genetic, biochemical, multi-omic, and nutritional evidence that riboflavin transport deficiency suppresses the oxidative phosphorylation and reprograms spermatozoa energy metabolism by disrupting flavoenzyme functions. Specifically, we find that fatty acid β-oxidation (FAO) is defective with significantly reduced levels of acyl-carnitines and metabolites from the TCA cycle (the citric acid cycle) but accumulated triglycerides and free fatty acids in Slc22a14 knockout spermatozoa. We demonstrate that Slc22a14-mediated FAO is essential for spermatozoa energy generation and motility. Furthermore, sperm from wild-type mice treated with a riboflavin-deficient diet mimics those in Slc22a14 knockout mice, confirming that an altered riboflavin level causes spermatozoa morphological and bioenergetic defects. Beyond substantially advancing our understanding of spermatozoa energy metabolism, our study provides an attractive target for the development of male contraceptives. Cell Press 2021-04-20 /pmc/articles/PMC8065176/ /pubmed/33882315 http://dx.doi.org/10.1016/j.celrep.2021.109025 Text en © 2021 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 Kuang, Wenhua Zhang, Jie Lan, Zhou Deepak, R.N.V. Krishna Liu, Chao Ma, Zhilong Cheng, Lili Zhao, Xinbin Meng, Xianbin Wang, Weihua Wang, Xueying Xu, Lina Jiao, Yupei Luo, Qi Meng, Ziyi Kee, Kehkooi Liu, Xiaohui Deng, Haiteng Li, Wei Fan, Hao Chen, Ligong SLC22A14 is a mitochondrial riboflavin transporter required for sperm oxidative phosphorylation and male fertility |
title | SLC22A14 is a mitochondrial riboflavin transporter required for sperm oxidative phosphorylation and male fertility |
title_full | SLC22A14 is a mitochondrial riboflavin transporter required for sperm oxidative phosphorylation and male fertility |
title_fullStr | SLC22A14 is a mitochondrial riboflavin transporter required for sperm oxidative phosphorylation and male fertility |
title_full_unstemmed | SLC22A14 is a mitochondrial riboflavin transporter required for sperm oxidative phosphorylation and male fertility |
title_short | SLC22A14 is a mitochondrial riboflavin transporter required for sperm oxidative phosphorylation and male fertility |
title_sort | slc22a14 is a mitochondrial riboflavin transporter required for sperm oxidative phosphorylation and male fertility |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065176/ https://www.ncbi.nlm.nih.gov/pubmed/33882315 http://dx.doi.org/10.1016/j.celrep.2021.109025 |
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