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Article

Sigma-1 Receptor Is Critical for Mitochondrial Activity and Unfolded Protein Response in Larval Zebrafish

MMDN, University of Montpellier, EPHE, INSERM, 34095 Montpellier, France
*
Author to whom correspondence should be addressed.
These authors contributed equally to the study.
Academic Editor: Joan Roselló-Catafau
Int. J. Mol. Sci. 2021, 22(20), 11049; https://doi.org/10.3390/ijms222011049
Received: 14 September 2021 / Revised: 6 October 2021 / Accepted: 10 October 2021 / Published: 13 October 2021
The sigma-1 receptor (S1R) is a highly conserved transmembrane protein highly enriched in mitochondria-associated endoplasmic reticulum (ER) membranes, where it interacts with several partners involved in ER-mitochondria Ca2+ transfer, activation of the ER stress pathways, and mitochondria function. We characterized a new S1R deficient zebrafish line and analyzed the impact of S1R deficiency on visual, auditory and locomotor functions. The s1r+25/+25 mutant line showed impairments in visual and locomotor functions compared to s1rWT. The locomotion of the s1r+25/+25 larvae, at 5 days post fertilization, was increased in the light and dark phases of the visual motor response. No deficit was observed in acoustic startle response. A critical role of S1R was shown in ER stress pathways and mitochondrial activity. Using qPCR to analyze the unfolded protein response genes, we observed that loss of S1R led to decreased levels of IRE1 and PERK-related effectors and increased over-expression of most of the effectors after a tunicamycin challenge. Finally, S1R deficiency led to alterations in mitochondria bioenergetics with decreased in basal, ATP-linked and non-mitochondrial respiration and following tunicamycin challenge. In conclusion, this new zebrafish model confirmed the importance of S1R activity on ER-mitochondria communication. It will be a useful tool to further analyze the physiopathological roles of S1R. View Full-Text
Keywords: sigma-1 receptor; phenotyping; zebrafish; ER stress; mitochondria bioenergetics sigma-1 receptor; phenotyping; zebrafish; ER stress; mitochondria bioenergetics
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MDPI and ACS Style

Crouzier, L.; Denus, M.; Richard, E.M.; Tavernier, A.; Diez, C.; Cubedo, N.; Maurice, T.; Delprat, B. Sigma-1 Receptor Is Critical for Mitochondrial Activity and Unfolded Protein Response in Larval Zebrafish. Int. J. Mol. Sci. 2021, 22, 11049. https://doi.org/10.3390/ijms222011049

AMA Style

Crouzier L, Denus M, Richard EM, Tavernier A, Diez C, Cubedo N, Maurice T, Delprat B. Sigma-1 Receptor Is Critical for Mitochondrial Activity and Unfolded Protein Response in Larval Zebrafish. International Journal of Molecular Sciences. 2021; 22(20):11049. https://doi.org/10.3390/ijms222011049

Chicago/Turabian Style

Crouzier, Lucie, Morgane Denus, Elodie M. Richard, Amarande Tavernier, Camille Diez, Nicolas Cubedo, Tangui Maurice, and Benjamin Delprat. 2021. "Sigma-1 Receptor Is Critical for Mitochondrial Activity and Unfolded Protein Response in Larval Zebrafish" International Journal of Molecular Sciences 22, no. 20: 11049. https://doi.org/10.3390/ijms222011049

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