PMID- 38534366
OWN - NLM
STAT- MEDLINE
DCOM- 20240328
LR  - 20240329
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 13
IP  - 6
DP  - 2024 Mar 16
TI  - Steroidogenesis Upregulation through Mitochondria-Associated Endoplasmic 
      Reticulum Membranes and Mitochondrial Dynamics in Rat Testes: The Role of 
      D-Aspartate.
LID - 10.3390/cells13060523 [doi]
LID - 523
AB  - 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.
FAU - Latino, Debora
AU  - Latino D
AUID- ORCID: 0000-0003-0757-8430
AD  - Department of Environmental, Biological and Pharmaceutical Sciences and 
      Technologies, University of Campania 'Luigi Vanvitelli', 81100 Caserta, Italy.
FAU - Venditti, Massimo
AU  - Venditti M
AUID- ORCID: 0000-0002-7357-5353
AD  - Department of Experimental Medicine, Section Human Physiology and Integrated 
      Biological Functions, University of Campania 'Luigi Vanvitelli', 80138 Napoli, 
      Italy.
FAU - Falvo, Sara
AU  - Falvo S
AD  - Department of Environmental, Biological and Pharmaceutical Sciences and 
      Technologies, University of Campania 'Luigi Vanvitelli', 81100 Caserta, Italy.
FAU - Grillo, Giulia
AU  - Grillo G
AD  - Department of Environmental, Biological and Pharmaceutical Sciences and 
      Technologies, University of Campania 'Luigi Vanvitelli', 81100 Caserta, Italy.
FAU - Santillo, Alessandra
AU  - Santillo A
AD  - Department of Environmental, Biological and Pharmaceutical Sciences and 
      Technologies, University of Campania 'Luigi Vanvitelli', 81100 Caserta, Italy.
FAU - Messaoudi, Imed
AU  - Messaoudi I
AUID- ORCID: 0000-0002-4025-8765
AD  - LR11ES41: Genetique, Biodiversite et Valorisation des Bioressources, Institut 
      Superieur de Biotechnologie, Universite de Monastir, Monastir 5000, Tunisia.
FAU - Ben Rhouma, Mariem
AU  - Ben Rhouma M
AD  - LR11ES41: Genetique, Biodiversite et Valorisation des Bioressources, Institut 
      Superieur de Biotechnologie, Universite de Monastir, Monastir 5000, Tunisia.
FAU - Minucci, Sergio
AU  - Minucci S
AUID- ORCID: 0000-0002-1007-7840
AD  - Department of Experimental Medicine, Section Human Physiology and Integrated 
      Biological Functions, University of Campania 'Luigi Vanvitelli', 80138 Napoli, 
      Italy.
FAU - Chieffi Baccari, Gabriella
AU  - Chieffi Baccari G
AD  - Department of Environmental, Biological and Pharmaceutical Sciences and 
      Technologies, University of Campania 'Luigi Vanvitelli', 81100 Caserta, Italy.
FAU - Di Fiore, Maria Maddalena
AU  - Di Fiore MM
AUID- ORCID: 0000-0003-4673-6729
AD  - Department of Environmental, Biological and Pharmaceutical Sciences and 
      Technologies, University of Campania 'Luigi Vanvitelli', 81100 Caserta, Italy.
LA  - eng
GR  - No to Sergio Minucci/PRIN 2020/
PT  - Journal Article
DEP - 20240316
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 4SR0Q8YD1X (D-Aspartic Acid)
RN  - 30KYC7MIAI (Aspartic Acid)
RN  - 0 (Lipids)
SB  - IM
MH  - Male
MH  - Rats
MH  - Animals
MH  - *Mitochondrial Membranes/metabolism
MH  - *Mitochondrial Dynamics
MH  - D-Aspartic Acid/pharmacology
MH  - Testis/metabolism
MH  - Up-Regulation
MH  - Aspartic Acid
MH  - Mitochondria/metabolism
MH  - Endoplasmic Reticulum/metabolism
MH  - Lipids/pharmacology
PMC - PMC10969159
OTO - NOTNLM
OT  - ER stress
OT  - biogenesis
OT  - calcium signaling
OT  - endoplasmic reticulum
OT  - fission
OT  - fusion
OT  - lipid traffic
OT  - mass
OT  - mitochondria
OT  - mitochondrial dynamics
OT  - steroidogenesis
COIS- The authors declare no conflict of interest.
EDAT- 2024/03/27 12:50
MHDA- 2024/03/28 06:46
PMCR- 2024/03/16
CRDT- 2024/03/27 09:24
PHST- 2024/01/30 00:00 [received]
PHST- 2024/03/14 00:00 [revised]
PHST- 2024/03/14 00:00 [accepted]
PHST- 2024/03/28 06:46 [medline]
PHST- 2024/03/27 12:50 [pubmed]
PHST- 2024/03/27 09:24 [entrez]
PHST- 2024/03/16 00:00 [pmc-release]
AID - cells13060523 [pii]
AID - cells-13-00523 [pii]
AID - 10.3390/cells13060523 [doi]
PST - epublish
SO  - Cells. 2024 Mar 16;13(6):523. doi: 10.3390/cells13060523.