Mitochondrial Fission Governed by Drp1 Regulates Exogenous Fatty Acid Usage and Storage in Hela Cells
In the presence of high abundance of exogenous fatty acids, cells either store fatty acids in lipid droplets or oxidize them in mitochondria. In this study, we aimed to explore a novel and direct role of mitochondrial fission in lipid homeostasis in HeLa cells. We observed the association between mi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/11/5/322 |
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| author | Jae-Eun Song Tiago C. Alves Bernardo Stutz Matija Šestan-Peša Nicole Kilian Sungho Jin Sabrina Diano Richard G. Kibbey Tamas L. Horvath |
| author_facet | Jae-Eun Song Tiago C. Alves Bernardo Stutz Matija Šestan-Peša Nicole Kilian Sungho Jin Sabrina Diano Richard G. Kibbey Tamas L. Horvath |
| author_sort | Jae-Eun Song |
| collection | DOAJ |
| description | In the presence of high abundance of exogenous fatty acids, cells either store fatty acids in lipid droplets or oxidize them in mitochondria. In this study, we aimed to explore a novel and direct role of mitochondrial fission in lipid homeostasis in HeLa cells. We observed the association between mitochondrial morphology and lipid droplet accumulation in response to high exogenous fatty acids. We inhibited mitochondrial fission by silencing dynamin-related protein 1(DRP1) and observed the shift in fatty acid storage-usage balance. Inhibition of mitochondrial fission resulted in an increase in fatty acid content of lipid droplets and a decrease in mitochondrial fatty acid oxidation. Next, we overexpressed carnitine palmitoyltransferase-1 (CPT1), a key mitochondrial protein in fatty acid oxidation, to further examine the relationship between mitochondrial fatty acid usage and mitochondrial morphology. Mitochondrial fission plays a role in distributing exogenous fatty acids. CPT1A controlled the respiratory rate of mitochondrial fatty acid oxidation but did not cause a shift in the distribution of fatty acids between mitochondria and lipid droplets. Our data reveals a novel function for mitochondrial fission in balancing exogenous fatty acids between usage and storage, assigning a role for mitochondrial dynamics in control of intracellular fuel utilization and partitioning. |
| first_indexed | 2024-03-10T11:19:08Z |
| format | Article |
| id | doaj.art-79220711625c484daab929828974ea71 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T11:19:08Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-79220711625c484daab929828974ea712023-11-21T20:10:24ZengMDPI AGMetabolites2218-19892021-05-0111532210.3390/metabo11050322Mitochondrial Fission Governed by Drp1 Regulates Exogenous Fatty Acid Usage and Storage in Hela CellsJae-Eun Song0Tiago C. Alves1Bernardo Stutz2Matija Šestan-Peša3Nicole Kilian4Sungho Jin5Sabrina Diano6Richard G. Kibbey7Tamas L. Horvath8Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06511, USALaboratory Medicine, Institute for Clinical Chemistry, Technische Universität Dresden, 01069 Dresden, GermanyYale Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06511, USAYale Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06511, USACentre for Infectious Diseases, Parasitology, Heidelberg University Hospital, 69120 Heidelberg, GermanyInstitute of Human Nutrition, Columbia University Irving Medical Center, New York, NY 10032, USAInstitute of Human Nutrition, Columbia University Irving Medical Center, New York, NY 10032, USADepartment of Internal Medicine, Yale University School of Medicine, New Haven, CT 06511, USAYale Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06511, USAIn the presence of high abundance of exogenous fatty acids, cells either store fatty acids in lipid droplets or oxidize them in mitochondria. In this study, we aimed to explore a novel and direct role of mitochondrial fission in lipid homeostasis in HeLa cells. We observed the association between mitochondrial morphology and lipid droplet accumulation in response to high exogenous fatty acids. We inhibited mitochondrial fission by silencing dynamin-related protein 1(DRP1) and observed the shift in fatty acid storage-usage balance. Inhibition of mitochondrial fission resulted in an increase in fatty acid content of lipid droplets and a decrease in mitochondrial fatty acid oxidation. Next, we overexpressed carnitine palmitoyltransferase-1 (CPT1), a key mitochondrial protein in fatty acid oxidation, to further examine the relationship between mitochondrial fatty acid usage and mitochondrial morphology. Mitochondrial fission plays a role in distributing exogenous fatty acids. CPT1A controlled the respiratory rate of mitochondrial fatty acid oxidation but did not cause a shift in the distribution of fatty acids between mitochondria and lipid droplets. Our data reveals a novel function for mitochondrial fission in balancing exogenous fatty acids between usage and storage, assigning a role for mitochondrial dynamics in control of intracellular fuel utilization and partitioning.https://www.mdpi.com/2218-1989/11/5/322mitochondrial dynamicsfatty acid oxidationlipid homeostasis |
| spellingShingle | Jae-Eun Song Tiago C. Alves Bernardo Stutz Matija Šestan-Peša Nicole Kilian Sungho Jin Sabrina Diano Richard G. Kibbey Tamas L. Horvath Mitochondrial Fission Governed by Drp1 Regulates Exogenous Fatty Acid Usage and Storage in Hela Cells Metabolites mitochondrial dynamics fatty acid oxidation lipid homeostasis |
| title | Mitochondrial Fission Governed by Drp1 Regulates Exogenous Fatty Acid Usage and Storage in Hela Cells |
| title_full | Mitochondrial Fission Governed by Drp1 Regulates Exogenous Fatty Acid Usage and Storage in Hela Cells |
| title_fullStr | Mitochondrial Fission Governed by Drp1 Regulates Exogenous Fatty Acid Usage and Storage in Hela Cells |
| title_full_unstemmed | Mitochondrial Fission Governed by Drp1 Regulates Exogenous Fatty Acid Usage and Storage in Hela Cells |
| title_short | Mitochondrial Fission Governed by Drp1 Regulates Exogenous Fatty Acid Usage and Storage in Hela Cells |
| title_sort | mitochondrial fission governed by drp1 regulates exogenous fatty acid usage and storage in hela cells |
| topic | mitochondrial dynamics fatty acid oxidation lipid homeostasis |
| url | https://www.mdpi.com/2218-1989/11/5/322 |
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