Steroidogenesis Upregulation through Mitochondria-Associated Endoplasmic Reticulum Membranes and Mitochondrial Dynamics in Rat Testes: The Role of D-Aspartate
Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs) mediate the communication between the Endoplasmic Reticulum (ER) and the mitochondria, playing a fundamental role in steroidogenesis. This study aimed to understand how D-aspartate (D-Asp), a well-known stimulator of testosterone biosynt...
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MDPI AG
2024-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/13/6/523 |
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| author | Debora Latino Massimo Venditti Sara Falvo Giulia Grillo Alessandra Santillo Imed Messaoudi Mariem Ben Rhouma Sergio Minucci Gabriella Chieffi Baccari Maria Maddalena Di Fiore |
| author_facet | Debora Latino Massimo Venditti Sara Falvo Giulia Grillo Alessandra Santillo Imed Messaoudi Mariem Ben Rhouma Sergio Minucci Gabriella Chieffi Baccari Maria Maddalena Di Fiore |
| author_sort | Debora Latino |
| collection | DOAJ |
| description | Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs) mediate the communication between the Endoplasmic Reticulum (ER) and the mitochondria, playing a fundamental role in steroidogenesis. This study aimed to understand how D-aspartate (D-Asp), a well-known stimulator of testosterone biosynthesis and spermatogenesis, affects the mechanism of steroidogenesis in rat testes. Our results suggested that D-Asp exerts this function through MAMs, affecting lipid trafficking, calcium signaling, ER stress, and mitochondrial dynamics. After 15 days of oral administration of D-Asp to rats, there was an increase in both antioxidant enzymes (SOD and Catalase) and in the protein expression levels of ATAD3A, FACL4, and SOAT1, which are markers of lipid transfer, as well as VDAC and GRP75, which are markers of calcium signaling. Additionally, there was a decrease in protein expression levels of GRP78, a marker of aging that counteracts ER stress. The effects of D-Asp on mitochondrial dynamics strongly suggested its active role as well. It induced the expression levels of proteins involved in fusion (MFN1, MFN2, and OPA1) and in biogenesis (NRF1 and TFAM), as well as in mitochondrial mass (TOMM20), and decreased the expression level of DRP1, a crucial mitochondrial fission marker. These findings suggested D-Asp involvement in the functional improvement of mitochondria during steroidogenesis. Immunofluorescent signals of ATAD3A, MFN1/2, TFAM, and TOMM20 confirmed their localization in Leydig cells showing an intensity upgrade in D-Asp-treated rat testes. Taken together, our results demonstrate the involvement of D-Asp in the steroidogenesis of rat testes, acting at multiple stages of both MAMs and mitochondrial dynamics, opening new opportunities for future investigation in other steroidogenic tissues. |
| first_indexed | 2024-04-24T18:26:32Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-04-24T18:26:32Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-25f933911afa467a865f48f110d78ab82024-03-27T13:30:39ZengMDPI AGCells2073-44092024-03-0113652310.3390/cells13060523Steroidogenesis Upregulation through Mitochondria-Associated Endoplasmic Reticulum Membranes and Mitochondrial Dynamics in Rat Testes: The Role of D-AspartateDebora Latino0Massimo Venditti1Sara Falvo2Giulia Grillo3Alessandra Santillo4Imed Messaoudi5Mariem Ben Rhouma6Sergio Minucci7Gabriella Chieffi Baccari8Maria Maddalena Di Fiore9Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania ‘Luigi Vanvitelli’, 81100 Caserta, ItalyDepartment of Experimental Medicine, Section Human Physiology and Integrated Biological Functions, University of Campania ‘Luigi Vanvitelli’, 80138 Napoli, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania ‘Luigi Vanvitelli’, 81100 Caserta, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania ‘Luigi Vanvitelli’, 81100 Caserta, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania ‘Luigi Vanvitelli’, 81100 Caserta, ItalyLR11ES41: Génetique, Biodiversité et Valorisation des Bioressources, Institut Supérieur de Biotechnologie, Université de Monastir, Monastir 5000, TunisiaLR11ES41: Génetique, Biodiversité et Valorisation des Bioressources, Institut Supérieur de Biotechnologie, Université de Monastir, Monastir 5000, TunisiaDepartment of Experimental Medicine, Section Human Physiology and Integrated Biological Functions, University of Campania ‘Luigi Vanvitelli’, 80138 Napoli, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania ‘Luigi Vanvitelli’, 81100 Caserta, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania ‘Luigi Vanvitelli’, 81100 Caserta, ItalyMitochondria-Associated Endoplasmic Reticulum Membranes (MAMs) mediate the communication between the Endoplasmic Reticulum (ER) and the mitochondria, playing a fundamental role in steroidogenesis. This study aimed to understand how D-aspartate (D-Asp), a well-known stimulator of testosterone biosynthesis and spermatogenesis, affects the mechanism of steroidogenesis in rat testes. Our results suggested that D-Asp exerts this function through MAMs, affecting lipid trafficking, calcium signaling, ER stress, and mitochondrial dynamics. After 15 days of oral administration of D-Asp to rats, there was an increase in both antioxidant enzymes (SOD and Catalase) and in the protein expression levels of ATAD3A, FACL4, and SOAT1, which are markers of lipid transfer, as well as VDAC and GRP75, which are markers of calcium signaling. Additionally, there was a decrease in protein expression levels of GRP78, a marker of aging that counteracts ER stress. The effects of D-Asp on mitochondrial dynamics strongly suggested its active role as well. It induced the expression levels of proteins involved in fusion (MFN1, MFN2, and OPA1) and in biogenesis (NRF1 and TFAM), as well as in mitochondrial mass (TOMM20), and decreased the expression level of DRP1, a crucial mitochondrial fission marker. These findings suggested D-Asp involvement in the functional improvement of mitochondria during steroidogenesis. Immunofluorescent signals of ATAD3A, MFN1/2, TFAM, and TOMM20 confirmed their localization in Leydig cells showing an intensity upgrade in D-Asp-treated rat testes. Taken together, our results demonstrate the involvement of D-Asp in the steroidogenesis of rat testes, acting at multiple stages of both MAMs and mitochondrial dynamics, opening new opportunities for future investigation in other steroidogenic tissues.https://www.mdpi.com/2073-4409/13/6/523endoplasmic reticulummitochondriasteroidogenesislipid trafficcalcium signalingER stress |
| spellingShingle | Debora Latino Massimo Venditti Sara Falvo Giulia Grillo Alessandra Santillo Imed Messaoudi Mariem Ben Rhouma Sergio Minucci Gabriella Chieffi Baccari Maria Maddalena Di Fiore Steroidogenesis Upregulation through Mitochondria-Associated Endoplasmic Reticulum Membranes and Mitochondrial Dynamics in Rat Testes: The Role of D-Aspartate Cells endoplasmic reticulum mitochondria steroidogenesis lipid traffic calcium signaling ER stress |
| title | Steroidogenesis Upregulation through Mitochondria-Associated Endoplasmic Reticulum Membranes and Mitochondrial Dynamics in Rat Testes: The Role of D-Aspartate |
| title_full | Steroidogenesis Upregulation through Mitochondria-Associated Endoplasmic Reticulum Membranes and Mitochondrial Dynamics in Rat Testes: The Role of D-Aspartate |
| title_fullStr | Steroidogenesis Upregulation through Mitochondria-Associated Endoplasmic Reticulum Membranes and Mitochondrial Dynamics in Rat Testes: The Role of D-Aspartate |
| title_full_unstemmed | Steroidogenesis Upregulation through Mitochondria-Associated Endoplasmic Reticulum Membranes and Mitochondrial Dynamics in Rat Testes: The Role of D-Aspartate |
| title_short | Steroidogenesis Upregulation through Mitochondria-Associated Endoplasmic Reticulum Membranes and Mitochondrial Dynamics in Rat Testes: The Role of D-Aspartate |
| title_sort | steroidogenesis upregulation through mitochondria associated endoplasmic reticulum membranes and mitochondrial dynamics in rat testes the role of d aspartate |
| topic | endoplasmic reticulum mitochondria steroidogenesis lipid traffic calcium signaling ER stress |
| url | https://www.mdpi.com/2073-4409/13/6/523 |
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