Expression of Synj2bp in mouse liver regulates the extent of wrappER-mitochondria contact to maintain hepatic lipid homeostasis
Abstract Background In mouse liver hepatocytes, nearly half of the surface area of every mitochondrion is covered by wrappER, a wrapping-type of ER that is rich in fatty acids and synthesizes lipoproteins (VLDL) (Anastasia et al. in Cell Rep 34:108873, 2021; Hurtley in Science (80- ) 372:142–143, 20...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Biology Direct |
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| Online Access: | https://doi.org/10.1186/s13062-022-00344-8 |
| _version_ | 1811207664358653952 |
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| author | Nicolò Ilacqua Irene Anastasia Danylo Aloshyn Rana Ghandehari-Alavijeh Emily Ann Peluso Madelaine C. Brearley-Sholto Leonardo V. Pellegrini Andrea Raimondi Thomas Q. de Aguiar Vallim Luca Pellegrini |
| author_facet | Nicolò Ilacqua Irene Anastasia Danylo Aloshyn Rana Ghandehari-Alavijeh Emily Ann Peluso Madelaine C. Brearley-Sholto Leonardo V. Pellegrini Andrea Raimondi Thomas Q. de Aguiar Vallim Luca Pellegrini |
| author_sort | Nicolò Ilacqua |
| collection | DOAJ |
| description | Abstract Background In mouse liver hepatocytes, nearly half of the surface area of every mitochondrion is covered by wrappER, a wrapping-type of ER that is rich in fatty acids and synthesizes lipoproteins (VLDL) (Anastasia et al. in Cell Rep 34:108873, 2021; Hurtley in Science (80- ) 372:142–143, 2021; Ilacqua et al. in J Cell Sci 135:1–11, 2021). A disruption of the ultrastructure of the wrappER-mitochondria contact results in altered fatty acid flux, leading to hepatic dyslipidemia (Anastasia et al. 2021). The molecular mechanism that regulates the extent of wrappER-mitochondria contacts is unknown. Methods We evaluated the expression level of the mitochondrial protein Synj2bp in the liver of normal and obese (ob/ob) mice. In addition, we silenced its expression in the liver using an AAV8 vector. We coupled quantitative EM morphometric analysis to proteomics and lipid analyses on these livers. Results The expression level of Synj2bp in the liver positively correlates with the extent of wrappER-mitochondria contacts. A 50% reduction in wrappER-mitochondria contacts causes hepatic dyslipidemia, characterized by a gross accumulation of lipid droplets in the liver, an increased hepatic secretion of VLDL and triglycerides, a curtailed ApoE expression, and an increased capacity of mitochondrial fatty acid respiration. Conclusion Synj2bp regulates the extent of wrappER-mitochondria contacts in the liver, thus contributing to the control of hepatic lipid flux. |
| first_indexed | 2024-04-12T04:08:42Z |
| format | Article |
| id | doaj.art-75a2382a6b0143c8aa3dbd7b1638baf2 |
| institution | Directory Open Access Journal |
| issn | 1745-6150 |
| language | English |
| last_indexed | 2024-04-12T04:08:42Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology Direct |
| spelling | doaj.art-75a2382a6b0143c8aa3dbd7b1638baf22022-12-22T03:48:33ZengBMCBiology Direct1745-61502022-12-0117111810.1186/s13062-022-00344-8Expression of Synj2bp in mouse liver regulates the extent of wrappER-mitochondria contact to maintain hepatic lipid homeostasisNicolò Ilacqua0Irene Anastasia1Danylo Aloshyn2Rana Ghandehari-Alavijeh3Emily Ann Peluso4Madelaine C. Brearley-Sholto5Leonardo V. Pellegrini6Andrea Raimondi7Thomas Q. de Aguiar Vallim8Luca Pellegrini9Graduate Program in Neuroscience, Faculty of Medicine, Laval UniversityMitochondria Biology Laboratory, Brain Research Center, Laval UniversityMitochondria Biology Laboratory, Brain Research Center, Laval UniversityMitochondria Biology Laboratory, Brain Research Center, Laval UniversityDepartments of Medicine/Cardiology and Biological Chemistry, University of CaliforniaDepartments of Medicine/Cardiology and Biological Chemistry, University of CaliforniaMitochondria Biology Laboratory, Brain Research Center, Laval UniversityExperimental Imaging Center, San Raffaele Scientific InstituteDepartments of Medicine/Cardiology and Biological Chemistry, University of CaliforniaMitochondria Biology Laboratory, Brain Research Center, Laval UniversityAbstract Background In mouse liver hepatocytes, nearly half of the surface area of every mitochondrion is covered by wrappER, a wrapping-type of ER that is rich in fatty acids and synthesizes lipoproteins (VLDL) (Anastasia et al. in Cell Rep 34:108873, 2021; Hurtley in Science (80- ) 372:142–143, 2021; Ilacqua et al. in J Cell Sci 135:1–11, 2021). A disruption of the ultrastructure of the wrappER-mitochondria contact results in altered fatty acid flux, leading to hepatic dyslipidemia (Anastasia et al. 2021). The molecular mechanism that regulates the extent of wrappER-mitochondria contacts is unknown. Methods We evaluated the expression level of the mitochondrial protein Synj2bp in the liver of normal and obese (ob/ob) mice. In addition, we silenced its expression in the liver using an AAV8 vector. We coupled quantitative EM morphometric analysis to proteomics and lipid analyses on these livers. Results The expression level of Synj2bp in the liver positively correlates with the extent of wrappER-mitochondria contacts. A 50% reduction in wrappER-mitochondria contacts causes hepatic dyslipidemia, characterized by a gross accumulation of lipid droplets in the liver, an increased hepatic secretion of VLDL and triglycerides, a curtailed ApoE expression, and an increased capacity of mitochondrial fatty acid respiration. Conclusion Synj2bp regulates the extent of wrappER-mitochondria contacts in the liver, thus contributing to the control of hepatic lipid flux.https://doi.org/10.1186/s13062-022-00344-8WrappERMitochondriaInter-organelle contactSynj2bpRrbp1ApoE |
| spellingShingle | Nicolò Ilacqua Irene Anastasia Danylo Aloshyn Rana Ghandehari-Alavijeh Emily Ann Peluso Madelaine C. Brearley-Sholto Leonardo V. Pellegrini Andrea Raimondi Thomas Q. de Aguiar Vallim Luca Pellegrini Expression of Synj2bp in mouse liver regulates the extent of wrappER-mitochondria contact to maintain hepatic lipid homeostasis Biology Direct WrappER Mitochondria Inter-organelle contact Synj2bp Rrbp1 ApoE |
| title | Expression of Synj2bp in mouse liver regulates the extent of wrappER-mitochondria contact to maintain hepatic lipid homeostasis |
| title_full | Expression of Synj2bp in mouse liver regulates the extent of wrappER-mitochondria contact to maintain hepatic lipid homeostasis |
| title_fullStr | Expression of Synj2bp in mouse liver regulates the extent of wrappER-mitochondria contact to maintain hepatic lipid homeostasis |
| title_full_unstemmed | Expression of Synj2bp in mouse liver regulates the extent of wrappER-mitochondria contact to maintain hepatic lipid homeostasis |
| title_short | Expression of Synj2bp in mouse liver regulates the extent of wrappER-mitochondria contact to maintain hepatic lipid homeostasis |
| title_sort | expression of synj2bp in mouse liver regulates the extent of wrapper mitochondria contact to maintain hepatic lipid homeostasis |
| topic | WrappER Mitochondria Inter-organelle contact Synj2bp Rrbp1 ApoE |
| url | https://doi.org/10.1186/s13062-022-00344-8 |
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