Effect of CB1 Receptor Deficiency on Mitochondrial Quality Control Pathways in Gastrocnemius Muscle

This study aims to explore the complex role of cannabinoid type 1 receptor (CB1) signaling in the gastrocnemius muscle, assessing physiological processes in both CB1<sup>+/+</sup> and CB1<sup>−/−</sup> mice. The primary focus is to enhance our understanding of how CB1 contrib...

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Main Authors: Rosalba Senese, Giuseppe Petito, Elena Silvestri, Maria Ventriglia, Nicola Mosca, Nicoletta Potenza, Aniello Russo, Francesco Manfrevola, Gilda Cobellis, Teresa Chioccarelli, Veronica Porreca, Vincenza Grazia Mele, Rosanna Chianese, Pieter de Lange, Giulia Ricci, Federica Cioffi, Antonia Lanni
Format: Article
Language:English
Published: MDPI AG 2024-02-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/13/2/116
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author Rosalba Senese
Giuseppe Petito
Elena Silvestri
Maria Ventriglia
Nicola Mosca
Nicoletta Potenza
Aniello Russo
Francesco Manfrevola
Gilda Cobellis
Teresa Chioccarelli
Veronica Porreca
Vincenza Grazia Mele
Rosanna Chianese
Pieter de Lange
Giulia Ricci
Federica Cioffi
Antonia Lanni
author_facet Rosalba Senese
Giuseppe Petito
Elena Silvestri
Maria Ventriglia
Nicola Mosca
Nicoletta Potenza
Aniello Russo
Francesco Manfrevola
Gilda Cobellis
Teresa Chioccarelli
Veronica Porreca
Vincenza Grazia Mele
Rosanna Chianese
Pieter de Lange
Giulia Ricci
Federica Cioffi
Antonia Lanni
author_sort Rosalba Senese
collection DOAJ
description This study aims to explore the complex role of cannabinoid type 1 receptor (CB1) signaling in the gastrocnemius muscle, assessing physiological processes in both CB1<sup>+/+</sup> and CB1<sup>−/−</sup> mice. The primary focus is to enhance our understanding of how CB1 contributes to mitochondrial homeostasis. At the tissue level, CB1<sup>−/−</sup> mice exhibit a substantial miRNA-related alteration in muscle fiber composition, characterized by an enrichment of oxidative fibers. CB1 absence induces a significant increase in the oxidative capacity of muscle, supported by elevated in-gel activity of Complex I and Complex IV of the mitochondrial respiratory chain. The increased oxidative capacity is associated with elevated oxidative stress and impaired antioxidant defense systems. Analysis of mitochondrial biogenesis markers indicates an enhanced capacity for new mitochondria production in CB1<sup>−/−</sup> mice, possibly adapting to altered muscle fiber composition. Changes in mitochondrial dynamics, mitophagy response, and unfolded protein response (UPR) pathways reveal a dynamic interplay in response to CB1 absence. The interconnected mitochondrial network, influenced by increased fusion and mitochondrial UPR components, underlines the dual role of CB1 in regulating both protein quality control and the generation of new mitochondria. These findings deepen our comprehension of the CB1 impact on muscle physiology, oxidative stress, and MQC processes, highlighting cellular adaptability to CB1<sup>−/−</sup>. This study paves the way for further exploration of intricate signaling cascades and cross-talk between cellular compartments in the context of CB1 and mitochondrial homeostasis.
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spelling doaj.art-43cd8a8545604357b204acebff3db2052024-02-23T15:08:13ZengMDPI AGBiology2079-77372024-02-0113211610.3390/biology13020116Effect of CB1 Receptor Deficiency on Mitochondrial Quality Control Pathways in Gastrocnemius MuscleRosalba Senese0Giuseppe Petito1Elena Silvestri2Maria Ventriglia3Nicola Mosca4Nicoletta Potenza5Aniello Russo6Francesco Manfrevola7Gilda Cobellis8Teresa Chioccarelli9Veronica Porreca10Vincenza Grazia Mele11Rosanna Chianese12Pieter de Lange13Giulia Ricci14Federica Cioffi15Antonia Lanni16Department 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 Sciences and Technologies, University of Sannio, 82100 Benevento, 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, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania “Luigi Vanvitelli”, 81100 Caserta, ItalyDepartment of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania “Luigi Vanvitelli”, 81100 Caserta, ItalyDepartment of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Sciences and Technologies, University of Sannio, 82100 Benevento, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania “Luigi Vanvitelli”, 81100 Caserta, ItalyThis study aims to explore the complex role of cannabinoid type 1 receptor (CB1) signaling in the gastrocnemius muscle, assessing physiological processes in both CB1<sup>+/+</sup> and CB1<sup>−/−</sup> mice. The primary focus is to enhance our understanding of how CB1 contributes to mitochondrial homeostasis. At the tissue level, CB1<sup>−/−</sup> mice exhibit a substantial miRNA-related alteration in muscle fiber composition, characterized by an enrichment of oxidative fibers. CB1 absence induces a significant increase in the oxidative capacity of muscle, supported by elevated in-gel activity of Complex I and Complex IV of the mitochondrial respiratory chain. The increased oxidative capacity is associated with elevated oxidative stress and impaired antioxidant defense systems. Analysis of mitochondrial biogenesis markers indicates an enhanced capacity for new mitochondria production in CB1<sup>−/−</sup> mice, possibly adapting to altered muscle fiber composition. Changes in mitochondrial dynamics, mitophagy response, and unfolded protein response (UPR) pathways reveal a dynamic interplay in response to CB1 absence. The interconnected mitochondrial network, influenced by increased fusion and mitochondrial UPR components, underlines the dual role of CB1 in regulating both protein quality control and the generation of new mitochondria. These findings deepen our comprehension of the CB1 impact on muscle physiology, oxidative stress, and MQC processes, highlighting cellular adaptability to CB1<sup>−/−</sup>. This study paves the way for further exploration of intricate signaling cascades and cross-talk between cellular compartments in the context of CB1 and mitochondrial homeostasis.https://www.mdpi.com/2079-7737/13/2/116cannabinoid type 1 receptor (CB1)skeletal musclemitochondriamitochondrial quality control (MQC)miRNAmitochondrial unfolded protein response (UPRmt)
spellingShingle Rosalba Senese
Giuseppe Petito
Elena Silvestri
Maria Ventriglia
Nicola Mosca
Nicoletta Potenza
Aniello Russo
Francesco Manfrevola
Gilda Cobellis
Teresa Chioccarelli
Veronica Porreca
Vincenza Grazia Mele
Rosanna Chianese
Pieter de Lange
Giulia Ricci
Federica Cioffi
Antonia Lanni
Effect of CB1 Receptor Deficiency on Mitochondrial Quality Control Pathways in Gastrocnemius Muscle
Biology
cannabinoid type 1 receptor (CB1)
skeletal muscle
mitochondria
mitochondrial quality control (MQC)
miRNA
mitochondrial unfolded protein response (UPRmt)
title Effect of CB1 Receptor Deficiency on Mitochondrial Quality Control Pathways in Gastrocnemius Muscle
title_full Effect of CB1 Receptor Deficiency on Mitochondrial Quality Control Pathways in Gastrocnemius Muscle
title_fullStr Effect of CB1 Receptor Deficiency on Mitochondrial Quality Control Pathways in Gastrocnemius Muscle
title_full_unstemmed Effect of CB1 Receptor Deficiency on Mitochondrial Quality Control Pathways in Gastrocnemius Muscle
title_short Effect of CB1 Receptor Deficiency on Mitochondrial Quality Control Pathways in Gastrocnemius Muscle
title_sort effect of cb1 receptor deficiency on mitochondrial quality control pathways in gastrocnemius muscle
topic cannabinoid type 1 receptor (CB1)
skeletal muscle
mitochondria
mitochondrial quality control (MQC)
miRNA
mitochondrial unfolded protein response (UPRmt)
url https://www.mdpi.com/2079-7737/13/2/116
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