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Neuronal Lipolysis Participates in PUFA‐mediated Neural Function and Neurodegeneration
Leilei Yang, Jingjing Liang, Sin Man Lam, Ahmet Yavuz, Guanghou Shui, Mei Ding, Xun Huang
EMBO Reports
Abstract
Lipid droplets (LDs) are dynamic cytoplasmic organelles present in most eukaryotic cells. The appearance of LDs in neurons is not usually observed under physiological conditions, but is associated with neural diseases. It remains unclear how LD dynamics is regulated in neurons and how the appearance of LDs affects neuronal functions. We discovered that mutations of two key lipolysis genes atgl‐1 and lid‐1 lead to LD appearance in neurons of Caenorhabditis elegans. This neuronal lipid accumulation protects neurons from hyperactivation‐triggered neurodegeneration, with a mild decrease in touch sensation. We also discovered that reduced biosynthesis of polyunsaturated fatty acids (PUFAs) causes similar effects and synergizes with decreased lipolysis. Furthermore, we demonstrated that these changes in lipolysis and PUFA biosynthesis increase PUFA partitioning toward triacylglycerol, and reduced incorporation of PUFAs into phospholipids increases neuronal protection. Together, these results suggest the crucial role of neuronal lipolysis in cell‐autonomous regulation of neural functions and neurodegeneration.
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论文编号: |
DOI:10.15252/embr.202050214 |
论文题目: |
Neuronal Lipolysis Participates in PUFA‐mediated Neural Function and Neurodegeneration |
英文论文题目: |
Neuronal Lipolysis Participates in PUFA‐mediated Neural Function and Neurodegeneration |
第一作者: |
Leilei Yang, Jingjing Liang, Sin Man Lam, Ahmet Yavuz, Guanghou Shui, Mei Ding, Xun Huang |
英文第一作者: |
Leilei Yang, Jingjing Liang, Sin Man Lam, Ahmet Yavuz, Guanghou Shui, Mei Ding, Xun Huang |
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2020-10-10 |
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摘要: |
Lipid droplets (LDs) are dynamic cytoplasmic organelles present in most eukaryotic cells. The appearance of LDs in neurons is not usually observed under physiological conditions, but is associated with neural diseases. It remains unclear how LD dynamics is regulated in neurons and how the appearance of LDs affects neuronal functions. We discovered that mutations of two key lipolysis genes atgl‐1 and lid‐1 lead to LD appearance in neurons of Caenorhabditis elegans. This neuronal lipid accumulation protects neurons from hyperactivation‐triggered neurodegeneration, with a mild decrease in touch sensation. We also discovered that reduced biosynthesis of polyunsaturated fatty acids (PUFAs) causes similar effects and synergizes with decreased lipolysis. Furthermore, we demonstrated that these changes in lipolysis and PUFA biosynthesis increase PUFA partitioning toward triacylglycerol, and reduced incorporation of PUFAs into phospholipids increases neuronal protection. Together, these results suggest the crucial role of neuronal lipolysis in cell‐autonomous regulation of neural functions and neurodegeneration. |
英文摘要: |
Lipid droplets (LDs) are dynamic cytoplasmic organelles present in most eukaryotic cells. The appearance of LDs in neurons is not usually observed under physiological conditions, but is associated with neural diseases. It remains unclear how LD dynamics is regulated in neurons and how the appearance of LDs affects neuronal functions. We discovered that mutations of two key lipolysis genes atgl‐1 and lid‐1 lead to LD appearance in neurons of Caenorhabditis elegans. This neuronal lipid accumulation protects neurons from hyperactivation‐triggered neurodegeneration, with a mild decrease in touch sensation. We also discovered that reduced biosynthesis of polyunsaturated fatty acids (PUFAs) causes similar effects and synergizes with decreased lipolysis. Furthermore, we demonstrated that these changes in lipolysis and PUFA biosynthesis increase PUFA partitioning toward triacylglycerol, and reduced incorporation of PUFAs into phospholipids increases neuronal protection. Together, these results suggest the crucial role of neuronal lipolysis in cell‐autonomous regulation of neural functions and neurodegeneration. |
刊物名称: |
EMBO Reports |
英文刊物名称: |
EMBO Reports |
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Leilei Yang, Jingjing Liang, Sin Man Lam, Ahmet Yavuz, Guanghou Shui, Mei Ding, Xun Huang. Neuronal Lipolysis Participates in PUFA‐mediated Neural Function and Neurodegeneration. EMBO Reports. DOI:10.15252/embr.202050214 |
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