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Updated: Sep 15, 2025
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Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
Published on: May 10, 2022
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FBXO24 targets SLC25A26 for K6-linked polyubiquitylation to maintain mitochondrial function during spermiogenesis
Yunlong Zheng1,2, Bingbing Wu2, Fucheng Dong2,3
1Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.
Development (Cambridge, England)
|July 14, 2025
Summary
FBXO24 is crucial for sperm mitochondrial function and ATP production, preventing male infertility. Its absence causes sperm defects by disrupting SLC25A26 stability, impacting motility.
Area of Science:
- Molecular Biology
- Reproductive Biology
- Cell Biology
Background:
- Asthenozoospermia, a key cause of male infertility, stems from sperm flagella and mitochondrial defects.
- The precise molecular mechanisms driving asthenozoospermia pathogenesis are not fully understood.
Purpose of the Study:
- To investigate the role of FBXO24 in spermiogenesis and mitochondrial function.
- To elucidate the pathogenic mechanisms of asthenozoospermia related to FBXO24.
Main Methods:
- Utilized Fbxo24 knockout mouse models.
- Employed quantitative proteomics to identify FBXO24 substrates.
- Analyzed mitochondrial function, ATP production, and sperm motility.
Main Results:
- FBXO24 deficiency in mice caused male infertility with sperm head malformations and motility defects.
- Mitochondrial dysfunction, including disorganized clustering, reduced membrane potential, and elevated ROS, was observed.
- Identified SLC25A26 as an FBXO24 substrate, with FBXO24 mediating its K6-linked polyubiquitylation and degradation.
Conclusions:
- FBXO24 maintains mitochondrial integrity and ATP production during spermiogenesis by regulating SLC25A26 stability.
- Dysfunctional FBXO24-mediated regulation of SLC25A26 impairs sperm motility and may contribute to human asthenozoospermia.
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