Neuronal Lipolysis Participates in PUFA-mediated Neural Function and Neurodegeneration

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2020 Oct 9

PMID 33034119

Citations 15

Authors

Leilei Yang

Jingjing Liang

Sin Man Lam

Ahmet Yavuz

Guanghou Shui

Mei Ding

Xun Huang

Affiliations

Soon will be listed here.

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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