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Updated: Apr 30, 2026

Author Spotlight: Advancing Male Infertility Research by Unraveling Sperm Metabolism and Mitochondrial Function
Published on: June 23, 2023
The role of mitochondrial aconitate (ACO2) in human sperm motility
Min Tang1, Bian-Jiang Liu, Shang-Qian Wang
1State Key Laboratory of Reproductive Medicine, Department of Urology, The First Affiliated Hospital of Nanjing Medical University , Nanjing , China and.
Abstract:
Deficiencies in tricarboxylic acid (TCA) cycle enzymes have been shown to cause a wide spectrum of human diseases, including malignancies and neurological and cardiac diseases. In mammalian spermatozoa mitochondria, the TCA cycle is known to be a crucial metabolic pathway that contributes to produce ATP. There is little known about the role and mechanism of mitochondrial aconitase (ACO2), which is an important regulatory enzyme of the TCA cycle, in asthenozoospermia. In the current study, immunofluorescence staining localized ACO2 to the human sperm mid-piece. By immunoblotting, we demonstrated that the level of ACO2 protein in asthenozoospermic samples was significantly decreased compared with that in normal fertile men. Importantly, we first observed that co-incubation of isocitrate with low motile sperm suspensions significantly improved sperm motility, which might be due to elevated intracellular ATP. The improvement of the sperm motility by isocitrate may have important clinical implications in the treatment of asthenozoospermia and certainly warrants further investigation.
Insights
Mitochondrial aconitase (ACO2) levels are reduced in asthenozoospermia. Supplementing with isocitrate improved sperm motility, suggesting a potential treatment for male infertility.
Area of Science:
- Biochemistry
- Human Physiology
- Reproductive Biology
Background:
- Tricarboxylic acid (TCA) cycle enzymes are vital for ATP production in sperm mitochondria.
- Mitochondrial aconitase (ACO2), a key TCA cycle enzyme, has an under-explored role in asthenozoospermia.
Purpose of the Study:
- To investigate the role and mechanism of ACO2 in human asthenozoospermia.
- To explore the potential of isocitrate as a therapeutic agent for improving sperm motility.
Main Methods:
- Immunofluorescence staining to localize ACO2 in human sperm.
- Immunoblotting to quantify ACO2 protein levels in asthenozoospermic and fertile samples.
- In vitro incubation of low-motile sperm with isocitrate to assess motility changes.
Main Results:
- ACO2 was localized to the mid-piece of human sperm.
- Asthenozoospermic samples showed significantly lower ACO2 protein levels compared to controls.
- Isocitrate incubation enhanced sperm motility in low-motile sperm suspensions, likely via increased ATP.
Conclusions:
- Reduced ACO2 protein levels are associated with asthenozoospermia.
- Isocitrate shows promise for improving sperm motility and may offer a novel therapeutic strategy for asthenozoospermia.
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