Myoglobin regulates fatty acid trafficking and lipid metabolism in mammary epithelial cells
Myoglobin (MB) is known to bind and deliver oxygen in striated muscles at high expression levels. MB is also expressed at much reduced levels in mammary epithelial cells, where the protein´s function is unclear. In this study, we aim to determine whether MB impacts fatty acid trafficking and facilit...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9555620/?tool=EBI |
| _version_ | 1811238941388439552 |
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| author | Julia Armbruster Mostafa A. Aboouf Max Gassmann Angela Egert Hubert Schorle Veit Hornung Tobias Schmidt Jonathan L. Schmid-Burgk Glen Kristiansen Anne Bicker Thomas Hankeln Hao Zhu Thomas A. Gorr |
| author_facet | Julia Armbruster Mostafa A. Aboouf Max Gassmann Angela Egert Hubert Schorle Veit Hornung Tobias Schmidt Jonathan L. Schmid-Burgk Glen Kristiansen Anne Bicker Thomas Hankeln Hao Zhu Thomas A. Gorr |
| author_sort | Julia Armbruster |
| collection | DOAJ |
| description | Myoglobin (MB) is known to bind and deliver oxygen in striated muscles at high expression levels. MB is also expressed at much reduced levels in mammary epithelial cells, where the protein´s function is unclear. In this study, we aim to determine whether MB impacts fatty acid trafficking and facilitates aerobic fatty acid ß-oxidation in mammary epithelial cells. We utilized MB-wildtype versus MB-knockout mice and human breast cancer cells to examine the impact of MB and its oxygenation status on fatty acid metabolism in mouse milk and mammary epithelia. MB deficient cells were generated through CRISPR/Cas9 and TALEN approaches and exposed to various oxygen tensions. Fatty acid profiling of milk and cell extracts were performed along with cell labelling and immunocytochemistry. Our findings show that MB expression in mammary epithelial cells promoted fatty acid oxidation while reducing stearyl-CoA desaturase activity for lipogenesis. In cells and milk product, presence of oxygenated MB significantly elevated indices of limited fatty acid ß-oxidation, i.e., the organelle-bound removal of a C2 moiety from long-chain saturated or monounsaturated fatty acids, thus shifting the composition toward more saturated and shorter fatty acid species. Presence of the globin also increased cytoplasmic fatty acid solubility under normoxia and fatty acid deposition to lipid droplets under severe hypoxia. We conclude that MB can function in mammary epithelia as intracellular O2-dependent shuttle of oxidizable fatty acid substrates. MB’s impact on limited oxidation of fatty acids could generate inflammatory mediator lipokines, such as 7-hexadecenoate. Thus, the novel functions of MB in breast epithelia described herein range from controlling fatty acid turnover and homeostasis to influencing inflammatory signalling cascade. Future work is needed to analyse to what extent these novel roles of MB also apply to myocytic cell physiology and malignant cell behaviour, respectively. |
| first_indexed | 2024-04-12T12:51:08Z |
| format | Article |
| id | doaj.art-034667929e304d02929e2820f85604a6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T12:51:08Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-034667929e304d02929e2820f85604a62022-12-22T03:32:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-011710Myoglobin regulates fatty acid trafficking and lipid metabolism in mammary epithelial cellsJulia ArmbrusterMostafa A. AbooufMax GassmannAngela EgertHubert SchorleVeit HornungTobias SchmidtJonathan L. Schmid-BurgkGlen KristiansenAnne BickerThomas HankelnHao ZhuThomas A. GorrMyoglobin (MB) is known to bind and deliver oxygen in striated muscles at high expression levels. MB is also expressed at much reduced levels in mammary epithelial cells, where the protein´s function is unclear. In this study, we aim to determine whether MB impacts fatty acid trafficking and facilitates aerobic fatty acid ß-oxidation in mammary epithelial cells. We utilized MB-wildtype versus MB-knockout mice and human breast cancer cells to examine the impact of MB and its oxygenation status on fatty acid metabolism in mouse milk and mammary epithelia. MB deficient cells were generated through CRISPR/Cas9 and TALEN approaches and exposed to various oxygen tensions. Fatty acid profiling of milk and cell extracts were performed along with cell labelling and immunocytochemistry. Our findings show that MB expression in mammary epithelial cells promoted fatty acid oxidation while reducing stearyl-CoA desaturase activity for lipogenesis. In cells and milk product, presence of oxygenated MB significantly elevated indices of limited fatty acid ß-oxidation, i.e., the organelle-bound removal of a C2 moiety from long-chain saturated or monounsaturated fatty acids, thus shifting the composition toward more saturated and shorter fatty acid species. Presence of the globin also increased cytoplasmic fatty acid solubility under normoxia and fatty acid deposition to lipid droplets under severe hypoxia. We conclude that MB can function in mammary epithelia as intracellular O2-dependent shuttle of oxidizable fatty acid substrates. MB’s impact on limited oxidation of fatty acids could generate inflammatory mediator lipokines, such as 7-hexadecenoate. Thus, the novel functions of MB in breast epithelia described herein range from controlling fatty acid turnover and homeostasis to influencing inflammatory signalling cascade. Future work is needed to analyse to what extent these novel roles of MB also apply to myocytic cell physiology and malignant cell behaviour, respectively.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9555620/?tool=EBI |
| spellingShingle | Julia Armbruster Mostafa A. Aboouf Max Gassmann Angela Egert Hubert Schorle Veit Hornung Tobias Schmidt Jonathan L. Schmid-Burgk Glen Kristiansen Anne Bicker Thomas Hankeln Hao Zhu Thomas A. Gorr Myoglobin regulates fatty acid trafficking and lipid metabolism in mammary epithelial cells PLoS ONE |
| title | Myoglobin regulates fatty acid trafficking and lipid metabolism in mammary epithelial cells |
| title_full | Myoglobin regulates fatty acid trafficking and lipid metabolism in mammary epithelial cells |
| title_fullStr | Myoglobin regulates fatty acid trafficking and lipid metabolism in mammary epithelial cells |
| title_full_unstemmed | Myoglobin regulates fatty acid trafficking and lipid metabolism in mammary epithelial cells |
| title_short | Myoglobin regulates fatty acid trafficking and lipid metabolism in mammary epithelial cells |
| title_sort | myoglobin regulates fatty acid trafficking and lipid metabolism in mammary epithelial cells |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9555620/?tool=EBI |
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