mTORC2 protects the heart from high-fat diet-induced cardiomyopathy through mitochondrial fission in Drosophila
High-fat diet (HFD)-induced obesity has become the major risk factor for the development of cardiovascular diseases, but the underlying mechanisms remain poorly understood. Here, we use Drosophila as a model to study the role of mTORC2 in HFD-induced mitochondrial fission and cardiac dysfunction. We...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.866210/full |
| _version_ | 1828363843576791040 |
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| author | Peiduo Liu Kai Chang Guillermo Requejo Hua Bai |
| author_facet | Peiduo Liu Kai Chang Guillermo Requejo Hua Bai |
| author_sort | Peiduo Liu |
| collection | DOAJ |
| description | High-fat diet (HFD)-induced obesity has become the major risk factor for the development of cardiovascular diseases, but the underlying mechanisms remain poorly understood. Here, we use Drosophila as a model to study the role of mTORC2 in HFD-induced mitochondrial fission and cardiac dysfunction. We find that knockdown of mTORC2 subunit rictor blocks HFD-induced mitochondrial fragmentation and Drp1 recruitment. Knockdown of rictor further impairs cardiac contractile function under HFD treatment. Surprisingly, knockdown of Akt, the major effector of mTORC2, did not affect HFD-induced mitochondrial fission. Similar to mTORC2 inhibition, knockdown of Drp1 blocks HFD-induced mitochondrial fragmentation and induces contractile defects. Furthermore, overexpression of Drp1 restored HFD-induced mitochondrial fragmentation in rictor knockdown flies. Thus, we uncover a novel function of mTORC2 in protecting the heart from HFD treatment through Drp1-dependent mitochondrial fission. |
| first_indexed | 2024-04-14T05:06:29Z |
| format | Article |
| id | doaj.art-6648e1508da143ac82945dc253be77bd |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-14T05:06:29Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-6648e1508da143ac82945dc253be77bd2022-12-22T02:10:40ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-07-011010.3389/fcell.2022.866210866210mTORC2 protects the heart from high-fat diet-induced cardiomyopathy through mitochondrial fission in DrosophilaPeiduo LiuKai ChangGuillermo RequejoHua BaiHigh-fat diet (HFD)-induced obesity has become the major risk factor for the development of cardiovascular diseases, but the underlying mechanisms remain poorly understood. Here, we use Drosophila as a model to study the role of mTORC2 in HFD-induced mitochondrial fission and cardiac dysfunction. We find that knockdown of mTORC2 subunit rictor blocks HFD-induced mitochondrial fragmentation and Drp1 recruitment. Knockdown of rictor further impairs cardiac contractile function under HFD treatment. Surprisingly, knockdown of Akt, the major effector of mTORC2, did not affect HFD-induced mitochondrial fission. Similar to mTORC2 inhibition, knockdown of Drp1 blocks HFD-induced mitochondrial fragmentation and induces contractile defects. Furthermore, overexpression of Drp1 restored HFD-induced mitochondrial fragmentation in rictor knockdown flies. Thus, we uncover a novel function of mTORC2 in protecting the heart from HFD treatment through Drp1-dependent mitochondrial fission.https://www.frontiersin.org/articles/10.3389/fcell.2022.866210/fullrictorDRP1Aktmitochondrial dynamicsmitochondrial homeostasisDrosophila cardiomyopathy |
| spellingShingle | Peiduo Liu Kai Chang Guillermo Requejo Hua Bai mTORC2 protects the heart from high-fat diet-induced cardiomyopathy through mitochondrial fission in Drosophila Frontiers in Cell and Developmental Biology rictor DRP1 Akt mitochondrial dynamics mitochondrial homeostasis Drosophila cardiomyopathy |
| title | mTORC2 protects the heart from high-fat diet-induced cardiomyopathy through mitochondrial fission in Drosophila |
| title_full | mTORC2 protects the heart from high-fat diet-induced cardiomyopathy through mitochondrial fission in Drosophila |
| title_fullStr | mTORC2 protects the heart from high-fat diet-induced cardiomyopathy through mitochondrial fission in Drosophila |
| title_full_unstemmed | mTORC2 protects the heart from high-fat diet-induced cardiomyopathy through mitochondrial fission in Drosophila |
| title_short | mTORC2 protects the heart from high-fat diet-induced cardiomyopathy through mitochondrial fission in Drosophila |
| title_sort | mtorc2 protects the heart from high fat diet induced cardiomyopathy through mitochondrial fission in drosophila |
| topic | rictor DRP1 Akt mitochondrial dynamics mitochondrial homeostasis Drosophila cardiomyopathy |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.866210/full |
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