2. Academic Validation
  3. The TEX44-CPT1B axis regulates mitochondrial sheath assembly and fatty acid oxidation in sperm

The TEX44-CPT1B axis regulates mitochondrial sheath assembly and fatty acid oxidation in sperm

  • Nat Commun. 2025 Aug 23;16(1):7864. doi: 10.1038/s41467-025-63280-x.
Erlei Zhi # 1,  Haowei Bai # 1,  Chuan Ren # 2,  Yue Dong # 2,  Jintao Zhang # 3,  Yanzhi Xu # 4 5 6,  Chen Tan # 7,  Yun Pan 2,  Lunni Zhou 4 5 6,  Peng Li 1,  Yueqiu Tan 7,  Yihong Zhou 8,  Lanlan Meng 7,  Junwei Xu 1,  Yuxiang Zhang 1,  Shuai Xu 1,  Zhiyong Ji 9,  Liangyu Zhao 10,  Min Jiang 11,  Zheng Li 1,  Chencheng Yao 1,  Yuchuan Zhou 12,  Jianping Wu 13 14 15,  Xiaoyu Yang 16,  Siyu Liu 17,  Mingxi Liu 18
Affiliations

Affiliations

  • 1 Shanghai Key Laboratory of Reproductive Medicine, Department of Andrology, Department of ART, Institute of Urology, Center for Men's Health, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Histology and Embryology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
  • 3 State Key Laboratory of Reproductive Medicine, The Center for Clinical Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 4 Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
  • 5 Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China.
  • 6 Institute of Biology, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China.
  • 7 NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Sciences, Central South University, Changsha, China.
  • 8 Department of Urology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
  • 9 Department of Reproductive Medicine, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
  • 10 Guangdong Provincial Key Laboratory of Biomedical Imaging, Department of Urology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, China.
  • 11 Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
  • 12 Shanghai Key Laboratory of Embryo Original Diseases, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. zhouych@sibcb.ac.cn.
  • 13 Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China. wujianping@westlake.edu.cn.
  • 14 Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China. wujianping@westlake.edu.cn.
  • 15 Institute of Biology, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China. wujianping@westlake.edu.cn.
  • 16 State Key Laboratory of Reproductive Medicine, The Center for Clinical Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. yxy1921@163.com.
  • 17 State Key Laboratory of Reproductive Medicine and Offspring Health, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Nanjing, China. njmulsy2017@126.com.
  • 18 State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Histology and Embryology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China. mingxi.liu@njmu.edu.cn.
  • # Contributed equally.
PMID: 40849303 DOI: 10.1038/s41467-025-63280-x
Abstract

Mitochondrial fatty acid β-oxidation (FAO) is essential for energy production and cellular homeostasis, yet its role in sperm function has remained unclear. Through whole-exome Sequencing (WES) of 800 patients with asthenozoospermia, we identified biallelic Testis-Expressed Protein 44 (TEX44) variants in six individuals, all of whom exhibited defective mitochondrial sheath assembly and impaired sperm motility. Using Tex44 knockout mice, we show that TEX44 interacts with carnitine palmitoyltransferase 1B (CPT1B) to form a mitochondrial glue, anchoring adjacent mitochondria and facilitating the assembly of the sperm-specific mitochondrial sheath. In vitro, we show that purified TEX44 protein can modulate CPT1B enzymatic activity, limiting the conversion of long-chain fatty acids such as palmitic acid and myristic acid into acyl-carnitines, thereby reducing Reactive Oxygen Species (ROS) production. Loss of TEX44 disrupts this regulatory mechanism, leading to unregulated FAO, excessive ROS generation, and severe oxidative damage to sperm DNA and flagellar structure. Additionally, germ cell-specific Cpt1b knockout mice exhibit phenotypes similar to TEX44 deficiency, including mitochondrial sheath defects and reduced sperm motility. These findings reveal a sperm-specific mechanism by which TEX44 regulates CPT1B activity to balance FAO and ROS generation, providing critical insights into energy metabolism, mitochondrial integrity, and male infertility.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z