Serine Availability Influences Mitochondrial Dynamics and Function through Lipid Metabolism
Summary: Cell proliferation can be dependent on the non-essential amino acid serine, and dietary restriction of serine inhibits tumor growth, but the underlying mechanisms remain incompletely understood. Using a metabolomics approach, we found that serine deprivation most predominantly impacts cellu...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-03-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718303462 |
| _version_ | 1818331203528294400 |
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| author | Xia Gao Katie Lee Michael A. Reid Sydney M. Sanderson Chuping Qiu Siqi Li Juan Liu Jason W. Locasale |
| author_facet | Xia Gao Katie Lee Michael A. Reid Sydney M. Sanderson Chuping Qiu Siqi Li Juan Liu Jason W. Locasale |
| author_sort | Xia Gao |
| collection | DOAJ |
| description | Summary: Cell proliferation can be dependent on the non-essential amino acid serine, and dietary restriction of serine inhibits tumor growth, but the underlying mechanisms remain incompletely understood. Using a metabolomics approach, we found that serine deprivation most predominantly impacts cellular acylcarnitine levels, a signature of altered mitochondrial function. Fuel utilization from fatty acid, glucose, and glutamine is affected by serine deprivation, as are mitochondrial morphological dynamics leading to increased fragmentation. Interestingly, these changes can occur independently of nucleotide and redox metabolism, two known major functions of serine. A lipidomics analysis revealed an overall decrease in ceramide levels. Importantly, supplementation of the lipid component of bovine serum or C16:0-ceramide could partially restore defects in cell proliferation and mitochondrial fragmentation induced by serine deprivation. Together, these data define a role for serine in supporting mitochondrial function and cell proliferation through ceramide metabolism. : Cell proliferation can be serine dependent, but the underlying mechanisms remain incompletely understood. Using metabolomic and lipidomic approaches, Gao et al. find that, in addition to their functional role in nucleotide and redox metabolism, serine-derived lipids, ceramides, are essential for mitochondrial function and cell proliferation. Keywords: serine, one carbon metabolism, mitochondria, ceramide, metabolism, sphingolipids, cell proliferation, mitochondrial dynamics |
| first_indexed | 2024-12-13T13:16:07Z |
| format | Article |
| id | doaj.art-2c631ef7ec4e4290901870d7e51d30bd |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T13:16:07Z |
| publishDate | 2018-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-2c631ef7ec4e4290901870d7e51d30bd2022-12-21T23:44:33ZengElsevierCell Reports2211-12472018-03-01221335073520Serine Availability Influences Mitochondrial Dynamics and Function through Lipid MetabolismXia Gao0Katie Lee1Michael A. Reid2Sydney M. Sanderson3Chuping Qiu4Siqi Li5Juan Liu6Jason W. Locasale7Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USADepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USADepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USADepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USADepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USADepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USADepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USADepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA; Corresponding authorSummary: Cell proliferation can be dependent on the non-essential amino acid serine, and dietary restriction of serine inhibits tumor growth, but the underlying mechanisms remain incompletely understood. Using a metabolomics approach, we found that serine deprivation most predominantly impacts cellular acylcarnitine levels, a signature of altered mitochondrial function. Fuel utilization from fatty acid, glucose, and glutamine is affected by serine deprivation, as are mitochondrial morphological dynamics leading to increased fragmentation. Interestingly, these changes can occur independently of nucleotide and redox metabolism, two known major functions of serine. A lipidomics analysis revealed an overall decrease in ceramide levels. Importantly, supplementation of the lipid component of bovine serum or C16:0-ceramide could partially restore defects in cell proliferation and mitochondrial fragmentation induced by serine deprivation. Together, these data define a role for serine in supporting mitochondrial function and cell proliferation through ceramide metabolism. : Cell proliferation can be serine dependent, but the underlying mechanisms remain incompletely understood. Using metabolomic and lipidomic approaches, Gao et al. find that, in addition to their functional role in nucleotide and redox metabolism, serine-derived lipids, ceramides, are essential for mitochondrial function and cell proliferation. Keywords: serine, one carbon metabolism, mitochondria, ceramide, metabolism, sphingolipids, cell proliferation, mitochondrial dynamicshttp://www.sciencedirect.com/science/article/pii/S2211124718303462 |
| spellingShingle | Xia Gao Katie Lee Michael A. Reid Sydney M. Sanderson Chuping Qiu Siqi Li Juan Liu Jason W. Locasale Serine Availability Influences Mitochondrial Dynamics and Function through Lipid Metabolism Cell Reports |
| title | Serine Availability Influences Mitochondrial Dynamics and Function through Lipid Metabolism |
| title_full | Serine Availability Influences Mitochondrial Dynamics and Function through Lipid Metabolism |
| title_fullStr | Serine Availability Influences Mitochondrial Dynamics and Function through Lipid Metabolism |
| title_full_unstemmed | Serine Availability Influences Mitochondrial Dynamics and Function through Lipid Metabolism |
| title_short | Serine Availability Influences Mitochondrial Dynamics and Function through Lipid Metabolism |
| title_sort | serine availability influences mitochondrial dynamics and function through lipid metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718303462 |
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