The impact of cannabinoid receptor 1 absence on mouse liver mitochondria homeostasis: insight into mitochondrial unfolded protein response
In the absence of CB1, several changes in the liver occur, including increased oxidative capacity, reduced complex I activity, enhanced complex IV activity, general upregulation of respiratory supercomplexes, as well as higher levels of oxidative stress. The mitochondria and cellular metabolism may be affected by these changes, increasing the risk of ROS-related damage. CB1<sup>-/-</sup> mice show upregulation of mitochondrial fusion, fission and biogenesis processes which suggests a dynamic response to the absence of CB1. Furthermore, oxidative stress disturbs mitochondrial proteostasis, initiating the mitochondrial unfolded protein response (UPR<sup>mt</sup>). We noted heightened levels of pivotal enzymes responsible for maintaining mitochondrial integrity, along with heightened expression of molecular chaperones and transcription factors associated with cellular stress reactions. Additionally, our discoveries demonstrate a synchronized reaction to cellular stress, involving both UPR<sup>mt</sup> and UPR<sup>ER</sup> pathways.
Authors
- Giulia Ricci (ORCID: https://orcid.org/0000-0002-2199-170X)
- Sara Falvo
- Veronica Porreca
- Gilda Cobellis (ORCID: https://orcid.org/0000-0001-5884-9208)
- Pieter de Lange (ORCID: https://orcid.org/0000-0002-5256-3599)
- Vincenza Grazia Mele
- Antonia Lanni (ORCID: https://orcid.org/0000-0001-5797-0348)
- Aniello Russo (ORCID: https://orcid.org/0000-0001-5421-3552)
- Rosanna Chianese (ORCID: https://orcid.org/0000-0003-3631-1794)
- Nicoletta Potenza (ORCID: https://orcid.org/0000-0002-9736-792X)
- Francesco Manfrevola (ORCID: https://orcid.org/0000-0003-0459-7644)
- Rosalba Senese (ORCID: https://orcid.org/0000-0003-1571-0980)
- Nicola Mosca (ORCID: https://orcid.org/0000-0003-0405-3807)
- Federica Cioffi (ORCID: https://orcid.org/0000-0002-1530-8556)
- Teresa Chioccarelli (ORCID: https://orcid.org/0000-0002-1720-1496)
- Giuseppe Petito (ORCID: https://orcid.org/0009-0006-5470-0354)
- Elena Silvestri (ORCID: https://orcid.org/0000-0002-0592-9033)
- Maria Ventriglia
Institutions
- University of Sannio (IT)
- University of Campania "Luigi Vanvitelli" (IT)
Publication Details
- Journal
- Frontiers in Cell and Developmental Biology
- Published
- 2024-10-24
- DOI
- https://doi.org/10.3389/fcell.2024.1464773
- Citations
- 4
- Primary Topic
- Cannabis and Cannabinoid Research
- Type
- article
- Field-Weighted Citation Impact
- 1.79
Funders
- Istituto Superiore di Sanità