Mitochondrial Oxidative Stress and Mitophagy Activation Contribute to TNF-Dependent Impairment of Myogenesis
Many muscular pathologies are associated with oxidative stress and elevated levels of the tumor necrosis factor (TNF) that cause muscle protein catabolism and impair myogenesis. Myogenesis defects caused by TNF are mediated in part by reactive oxygen species (ROS), including those produced by mitoch...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/12/3/602 |
| _version_ | 1797613797793333248 |
|---|---|
| author | Daniil A. Chernyavskij Olga Yu. Pletjushkina Anastasia V. Kashtanova Ivan I. Galkin Anna Karpukhina Boris V. Chernyak Yegor S. Vassetzky Ekaterina N. Popova |
| author_facet | Daniil A. Chernyavskij Olga Yu. Pletjushkina Anastasia V. Kashtanova Ivan I. Galkin Anna Karpukhina Boris V. Chernyak Yegor S. Vassetzky Ekaterina N. Popova |
| author_sort | Daniil A. Chernyavskij |
| collection | DOAJ |
| description | Many muscular pathologies are associated with oxidative stress and elevated levels of the tumor necrosis factor (TNF) that cause muscle protein catabolism and impair myogenesis. Myogenesis defects caused by TNF are mediated in part by reactive oxygen species (ROS), including those produced by mitochondria (mitoROS), but the mechanism of their pathological action is not fully understood. We hypothesized that mitoROS act by triggering and enhancing mitophagy, an important tool for remodelling the mitochondrial reticulum during myogenesis. We used three recently developed probes—MitoTracker Orange CM-H2TMRos, mito-QC, and MitoCLox—to study myogenesis in human myoblasts. Induction of myogenesis resulted in a significant increase in mitoROS generation and phospholipid peroxidation in the inner mitochondrial membrane, as well as mitophagy enhancement. Treatment of myoblasts with TNF 24 h before induction of myogenesis resulted in a significant decrease in the myoblast fusion index and myosin heavy chain (MYH2) synthesis. TNF increased the levels of mitoROS, phospholipid peroxidation in the inner mitochondrial membrane and mitophagy at an early stage of differentiation. Trolox and SkQ1 antioxidants partially restored TNF-impaired myogenesis. The general autophagy inducers rapamycin and AICAR, which also stimulate mitophagy, completely blocked myogenesis. The autophagy suppression by the ULK1 inhibitor SBI-0206965 partially restored myogenesis impaired by TNF. Thus, suppression of myogenesis by TNF is associated with a mitoROS-dependent increase in general autophagy and mitophagy. |
| first_indexed | 2024-03-11T07:00:43Z |
| format | Article |
| id | doaj.art-94462601efd44b7e802a994476d91685 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T07:00:43Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-94462601efd44b7e802a994476d916852023-11-17T09:17:14ZengMDPI AGAntioxidants2076-39212023-03-0112360210.3390/antiox12030602Mitochondrial Oxidative Stress and Mitophagy Activation Contribute to TNF-Dependent Impairment of MyogenesisDaniil A. Chernyavskij0Olga Yu. Pletjushkina1Anastasia V. Kashtanova2Ivan I. Galkin3Anna Karpukhina4Boris V. Chernyak5Yegor S. Vassetzky6Ekaterina N. Popova7Belozersky Institute of Physico-Chemical Biology, 119992 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, 119992 Moscow, RussiaFaculty of Bioengineering and Bioinformatics, Moscow State University, 119992 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, 119992 Moscow, RussiaKoltzov Institute of Developmental Biology, 117334 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, 119992 Moscow, RussiaKoltzov Institute of Developmental Biology, 117334 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, 119992 Moscow, RussiaMany muscular pathologies are associated with oxidative stress and elevated levels of the tumor necrosis factor (TNF) that cause muscle protein catabolism and impair myogenesis. Myogenesis defects caused by TNF are mediated in part by reactive oxygen species (ROS), including those produced by mitochondria (mitoROS), but the mechanism of their pathological action is not fully understood. We hypothesized that mitoROS act by triggering and enhancing mitophagy, an important tool for remodelling the mitochondrial reticulum during myogenesis. We used three recently developed probes—MitoTracker Orange CM-H2TMRos, mito-QC, and MitoCLox—to study myogenesis in human myoblasts. Induction of myogenesis resulted in a significant increase in mitoROS generation and phospholipid peroxidation in the inner mitochondrial membrane, as well as mitophagy enhancement. Treatment of myoblasts with TNF 24 h before induction of myogenesis resulted in a significant decrease in the myoblast fusion index and myosin heavy chain (MYH2) synthesis. TNF increased the levels of mitoROS, phospholipid peroxidation in the inner mitochondrial membrane and mitophagy at an early stage of differentiation. Trolox and SkQ1 antioxidants partially restored TNF-impaired myogenesis. The general autophagy inducers rapamycin and AICAR, which also stimulate mitophagy, completely blocked myogenesis. The autophagy suppression by the ULK1 inhibitor SBI-0206965 partially restored myogenesis impaired by TNF. Thus, suppression of myogenesis by TNF is associated with a mitoROS-dependent increase in general autophagy and mitophagy.https://www.mdpi.com/2076-3921/12/3/602TNFmyogenesismitochondriareactive oxygen species (ROS)mitophagyantioxidant |
| spellingShingle | Daniil A. Chernyavskij Olga Yu. Pletjushkina Anastasia V. Kashtanova Ivan I. Galkin Anna Karpukhina Boris V. Chernyak Yegor S. Vassetzky Ekaterina N. Popova Mitochondrial Oxidative Stress and Mitophagy Activation Contribute to TNF-Dependent Impairment of Myogenesis Antioxidants TNF myogenesis mitochondria reactive oxygen species (ROS) mitophagy antioxidant |
| title | Mitochondrial Oxidative Stress and Mitophagy Activation Contribute to TNF-Dependent Impairment of Myogenesis |
| title_full | Mitochondrial Oxidative Stress and Mitophagy Activation Contribute to TNF-Dependent Impairment of Myogenesis |
| title_fullStr | Mitochondrial Oxidative Stress and Mitophagy Activation Contribute to TNF-Dependent Impairment of Myogenesis |
| title_full_unstemmed | Mitochondrial Oxidative Stress and Mitophagy Activation Contribute to TNF-Dependent Impairment of Myogenesis |
| title_short | Mitochondrial Oxidative Stress and Mitophagy Activation Contribute to TNF-Dependent Impairment of Myogenesis |
| title_sort | mitochondrial oxidative stress and mitophagy activation contribute to tnf dependent impairment of myogenesis |
| topic | TNF myogenesis mitochondria reactive oxygen species (ROS) mitophagy antioxidant |
| url | https://www.mdpi.com/2076-3921/12/3/602 |
| work_keys_str_mv | AT daniilachernyavskij mitochondrialoxidativestressandmitophagyactivationcontributetotnfdependentimpairmentofmyogenesis AT olgayupletjushkina mitochondrialoxidativestressandmitophagyactivationcontributetotnfdependentimpairmentofmyogenesis AT anastasiavkashtanova mitochondrialoxidativestressandmitophagyactivationcontributetotnfdependentimpairmentofmyogenesis AT ivanigalkin mitochondrialoxidativestressandmitophagyactivationcontributetotnfdependentimpairmentofmyogenesis AT annakarpukhina mitochondrialoxidativestressandmitophagyactivationcontributetotnfdependentimpairmentofmyogenesis AT borisvchernyak mitochondrialoxidativestressandmitophagyactivationcontributetotnfdependentimpairmentofmyogenesis AT yegorsvassetzky mitochondrialoxidativestressandmitophagyactivationcontributetotnfdependentimpairmentofmyogenesis AT ekaterinanpopova mitochondrialoxidativestressandmitophagyactivationcontributetotnfdependentimpairmentofmyogenesis |