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Mitochondrial uncoupling proteins regulate the metabolic function of human Sertoli cells
David F Carrageta1,2, Laís Freire-Brito1,2, Bárbara Guerra-Carvalho1,2,3,4
1Clinical and Experimental Endocrinology, UMIB - Unit for Multidisciplinary Research in Biomedicine, ICBAS - School of Medicine and Biomedical Sciences, University of Porto, Rua Jorge de Viterbo Ferreira 228, Porto, Portugal.
Reproduction (Cambridge, England)
|November 29, 2023
Summary
Mitochondrial uncoupling proteins (UCPs) regulate mitochondrial activity in human Sertoli cells. Their inhibition impacts cell proliferation, mitochondrial function, and metabolism, suggesting UCPs are key targets for male infertility research.
Area of Science:
- Cell Biology
- Mitochondrial Biology
- Reproductive Biology
Background:
- Mitochondrial uncoupling proteins (UCPs) are crucial for regulating mitochondrial activity and reactive oxygen species (ROS) production.
- Dysfunctional UCPs are linked to mitochondrial dysfunction and oxidative stress, contributing to male infertility.
- UCP expression and function in the human testis are not well-characterized.
Purpose of the Study:
- To investigate the expression and function of UCP homologs (UCP1-6) in human Sertoli cells (hSCs).
- To determine the role of UCPs in modulating mitochondrial activity and metabolism in hSCs.
- To explore the potential of UCPs as therapeutic targets for male infertility.
Main Methods:
- Primary cultures of human Sertoli cells (hSCs) were used.
- mRNA and protein expression of UCP homologs (UCP1-6) were analyzed.
- UCP function was inhibited using genipin, and effects on cell proliferation, mitochondrial membrane potential, oxygen consumption rate (OCR), ROS production, and cellular metabolism were assessed.
Main Results:
- All UCP homologs (UCP1-6) showed mRNA expression in hSCs, with UCP1, UCP2, and UCP3 also detected at the protein level.
- UCP inhibition by genipin reduced hSC proliferation without inducing cytotoxicity.
- Prolonged UCP inhibition decreased mitochondrial membrane potential, OCR, and endogenous ROS production, while increasing pyruvate consumption, indicating a metabolic shift.
Conclusions:
- UCPs are expressed in human Sertoli cells and play a significant role in regulating mitochondrial function and metabolism.
- These findings highlight UCPs as critical modulators of mitochondrial activity in hSCs.
- UCPs represent potential targets for understanding and treating male infertility.
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