All-Trans Retinoic Acid Increases DRP1 Levels and Promotes Mitochondrial Fission
In the heart, mitochondrial homeostasis is critical for sustaining normal function and optimal responses to metabolic and environmental stressors. Mitochondrial fusion and fission are thought to be necessary for maintaining a robust population of mitochondria, and disruptions in mitochondrial fissio...
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MDPI AG
2021-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/5/1202 |
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| author | Bojjibabu Chidipi Syed Islamuddin Shah Michelle Reiser Manasa Kanithi Amanda Garces Byeong J. Cha Ghanim Ullah Sami F. Noujaim |
| author_facet | Bojjibabu Chidipi Syed Islamuddin Shah Michelle Reiser Manasa Kanithi Amanda Garces Byeong J. Cha Ghanim Ullah Sami F. Noujaim |
| author_sort | Bojjibabu Chidipi |
| collection | DOAJ |
| description | In the heart, mitochondrial homeostasis is critical for sustaining normal function and optimal responses to metabolic and environmental stressors. Mitochondrial fusion and fission are thought to be necessary for maintaining a robust population of mitochondria, and disruptions in mitochondrial fission and/or fusion can lead to cellular dysfunction. The dynamin-related protein (DRP1) is an important mediator of mitochondrial fission. In this study, we investigated the direct effects of the micronutrient retinoid all-trans retinoic acid (ATRA) on the mitochondrial structure in vivo and in vitro using Western blot, confocal, and transmission electron microscopy, as well as mitochondrial network quantification using stochastic modeling. Our results showed that ATRA increases DRP1 protein levels, increases the localization of DRP1 to mitochondria in isolated mitochondrial preparations. Our results also suggested that ATRA remodels the mitochondrial ultrastructure where the mitochondrial area and perimeter were decreased and the circularity was increased. Microscopically, mitochondrial network remodeling is driven by an increased rate of fission over fusion events in ATRA, as suggested by our numerical modeling. In conclusion, ATRA results in a pharmacologically mediated increase in the DRP1 protein. It also results in the modulation of cardiac mitochondria by promoting fission events, altering the mitochondrial network, and modifying the ultrastructure of mitochondria in the heart. |
| first_indexed | 2024-03-10T11:25:13Z |
| format | Article |
| id | doaj.art-d02aa3fdae3e4f77a62e01fcf8b723ec |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T11:25:13Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-d02aa3fdae3e4f77a62e01fcf8b723ec2023-11-21T19:42:56ZengMDPI AGCells2073-44092021-05-01105120210.3390/cells10051202All-Trans Retinoic Acid Increases DRP1 Levels and Promotes Mitochondrial FissionBojjibabu Chidipi0Syed Islamuddin Shah1Michelle Reiser2Manasa Kanithi3Amanda Garces4Byeong J. Cha5Ghanim Ullah6Sami F. Noujaim7Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USADepartment of Physics, University of South Florida, Tampa, FL 33620, USADepartment of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USADepartment of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USALisa Muma Weitz Laboratory for Advanced Microscopy & Cell Imaging, University of South Florida, Tampa, FL 33612, USADepartment of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USADepartment of Physics, University of South Florida, Tampa, FL 33620, USADepartment of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USAIn the heart, mitochondrial homeostasis is critical for sustaining normal function and optimal responses to metabolic and environmental stressors. Mitochondrial fusion and fission are thought to be necessary for maintaining a robust population of mitochondria, and disruptions in mitochondrial fission and/or fusion can lead to cellular dysfunction. The dynamin-related protein (DRP1) is an important mediator of mitochondrial fission. In this study, we investigated the direct effects of the micronutrient retinoid all-trans retinoic acid (ATRA) on the mitochondrial structure in vivo and in vitro using Western blot, confocal, and transmission electron microscopy, as well as mitochondrial network quantification using stochastic modeling. Our results showed that ATRA increases DRP1 protein levels, increases the localization of DRP1 to mitochondria in isolated mitochondrial preparations. Our results also suggested that ATRA remodels the mitochondrial ultrastructure where the mitochondrial area and perimeter were decreased and the circularity was increased. Microscopically, mitochondrial network remodeling is driven by an increased rate of fission over fusion events in ATRA, as suggested by our numerical modeling. In conclusion, ATRA results in a pharmacologically mediated increase in the DRP1 protein. It also results in the modulation of cardiac mitochondria by promoting fission events, altering the mitochondrial network, and modifying the ultrastructure of mitochondria in the heart.https://www.mdpi.com/2073-4409/10/5/1202all-trans retinoic acidDRP1mitochondrial fusionmitochondrial fissionmitochondrial network |
| spellingShingle | Bojjibabu Chidipi Syed Islamuddin Shah Michelle Reiser Manasa Kanithi Amanda Garces Byeong J. Cha Ghanim Ullah Sami F. Noujaim All-Trans Retinoic Acid Increases DRP1 Levels and Promotes Mitochondrial Fission Cells all-trans retinoic acid DRP1 mitochondrial fusion mitochondrial fission mitochondrial network |
| title | All-Trans Retinoic Acid Increases DRP1 Levels and Promotes Mitochondrial Fission |
| title_full | All-Trans Retinoic Acid Increases DRP1 Levels and Promotes Mitochondrial Fission |
| title_fullStr | All-Trans Retinoic Acid Increases DRP1 Levels and Promotes Mitochondrial Fission |
| title_full_unstemmed | All-Trans Retinoic Acid Increases DRP1 Levels and Promotes Mitochondrial Fission |
| title_short | All-Trans Retinoic Acid Increases DRP1 Levels and Promotes Mitochondrial Fission |
| title_sort | all trans retinoic acid increases drp1 levels and promotes mitochondrial fission |
| topic | all-trans retinoic acid DRP1 mitochondrial fusion mitochondrial fission mitochondrial network |
| url | https://www.mdpi.com/2073-4409/10/5/1202 |
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