Mitochondrial Permeability Transition Causes Mitochondrial Reactive Oxygen Species- and Caspase 3-Dependent Atrophy of Single Adult Mouse Skeletal Muscle Fibers
Elevated mitochondrial reactive oxygen species (mROS) and an increase in caspase-3 activity are established mechanisms that lead to skeletal muscle atrophy via the upregulation of protein degradation pathways. However, the mechanisms upstream of an increase in mROS and caspase-3 activity in conditio...
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MDPI AG
2021-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/10/2586 |
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| author | Sarah K. Skinner Angelo Solania Dennis W. Wolan Michael S. Cohen Terence E. Ryan Russell T. Hepple |
| author_facet | Sarah K. Skinner Angelo Solania Dennis W. Wolan Michael S. Cohen Terence E. Ryan Russell T. Hepple |
| author_sort | Sarah K. Skinner |
| collection | DOAJ |
| description | Elevated mitochondrial reactive oxygen species (mROS) and an increase in caspase-3 activity are established mechanisms that lead to skeletal muscle atrophy via the upregulation of protein degradation pathways. However, the mechanisms upstream of an increase in mROS and caspase-3 activity in conditions of muscle atrophy have not been identified. Based upon knowledge that an event known as mitochondrial permeability transition (MPT) causes an increase in mROS emission and the activation of caspase-3 via mitochondrial release of cytochrome c, as well as the circumstantial evidence for MPT in some muscle atrophy conditions, we tested MPT as a mechanism of atrophy. Briefly, treating cultured single mouse flexor digitorum brevis (FDB) fibers from adult mice with a chemical inducer of MPT (Bz423) for 24 h caused an increase in mROS and caspase-3 activity that was accompanied by a reduction in muscle fiber diameter that was able to be prevented by inhibitors of MPT, mROS, or caspase-3 (<i>p</i> < 0.05). Similarly, a four-day single fiber culture as a model of disuse caused atrophy that could be prevented by inhibitors of MPT, mROS, or activated caspase-3. As such, our results identify MPT as a novel mechanism of skeletal muscle atrophy that operates through mROS emission and caspase-3 activation. |
| first_indexed | 2024-03-10T06:39:32Z |
| format | Article |
| id | doaj.art-703073fe695c4d14a606e6e51d47d57a |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T06:39:32Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-703073fe695c4d14a606e6e51d47d57a2023-11-22T17:45:59ZengMDPI AGCells2073-44092021-09-011010258610.3390/cells10102586Mitochondrial Permeability Transition Causes Mitochondrial Reactive Oxygen Species- and Caspase 3-Dependent Atrophy of Single Adult Mouse Skeletal Muscle FibersSarah K. Skinner0Angelo Solania1Dennis W. Wolan2Michael S. Cohen3Terence E. Ryan4Russell T. Hepple5Department of Physical Therapy, University of Florida, Gainesville, FL 32610, USADepartments of Molecular Medicine and Integrative Structural and Computational Biology, Scripps Research, La Jolla, San Diego, CA 92037, USADepartments of Molecular Medicine and Integrative Structural and Computational Biology, Scripps Research, La Jolla, San Diego, CA 92037, USADepartment of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, OR 97239, USADepartment of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32610, USADepartment of Physical Therapy, University of Florida, Gainesville, FL 32610, USAElevated mitochondrial reactive oxygen species (mROS) and an increase in caspase-3 activity are established mechanisms that lead to skeletal muscle atrophy via the upregulation of protein degradation pathways. However, the mechanisms upstream of an increase in mROS and caspase-3 activity in conditions of muscle atrophy have not been identified. Based upon knowledge that an event known as mitochondrial permeability transition (MPT) causes an increase in mROS emission and the activation of caspase-3 via mitochondrial release of cytochrome c, as well as the circumstantial evidence for MPT in some muscle atrophy conditions, we tested MPT as a mechanism of atrophy. Briefly, treating cultured single mouse flexor digitorum brevis (FDB) fibers from adult mice with a chemical inducer of MPT (Bz423) for 24 h caused an increase in mROS and caspase-3 activity that was accompanied by a reduction in muscle fiber diameter that was able to be prevented by inhibitors of MPT, mROS, or caspase-3 (<i>p</i> < 0.05). Similarly, a four-day single fiber culture as a model of disuse caused atrophy that could be prevented by inhibitors of MPT, mROS, or activated caspase-3. As such, our results identify MPT as a novel mechanism of skeletal muscle atrophy that operates through mROS emission and caspase-3 activation.https://www.mdpi.com/2073-4409/10/10/2586mitochondrial permeability transition poreROScaspase-3skeletal muscle atrophy |
| spellingShingle | Sarah K. Skinner Angelo Solania Dennis W. Wolan Michael S. Cohen Terence E. Ryan Russell T. Hepple Mitochondrial Permeability Transition Causes Mitochondrial Reactive Oxygen Species- and Caspase 3-Dependent Atrophy of Single Adult Mouse Skeletal Muscle Fibers Cells mitochondrial permeability transition pore ROS caspase-3 skeletal muscle atrophy |
| title | Mitochondrial Permeability Transition Causes Mitochondrial Reactive Oxygen Species- and Caspase 3-Dependent Atrophy of Single Adult Mouse Skeletal Muscle Fibers |
| title_full | Mitochondrial Permeability Transition Causes Mitochondrial Reactive Oxygen Species- and Caspase 3-Dependent Atrophy of Single Adult Mouse Skeletal Muscle Fibers |
| title_fullStr | Mitochondrial Permeability Transition Causes Mitochondrial Reactive Oxygen Species- and Caspase 3-Dependent Atrophy of Single Adult Mouse Skeletal Muscle Fibers |
| title_full_unstemmed | Mitochondrial Permeability Transition Causes Mitochondrial Reactive Oxygen Species- and Caspase 3-Dependent Atrophy of Single Adult Mouse Skeletal Muscle Fibers |
| title_short | Mitochondrial Permeability Transition Causes Mitochondrial Reactive Oxygen Species- and Caspase 3-Dependent Atrophy of Single Adult Mouse Skeletal Muscle Fibers |
| title_sort | mitochondrial permeability transition causes mitochondrial reactive oxygen species and caspase 3 dependent atrophy of single adult mouse skeletal muscle fibers |
| topic | mitochondrial permeability transition pore ROS caspase-3 skeletal muscle atrophy |
| url | https://www.mdpi.com/2073-4409/10/10/2586 |
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