The endoribonuclease Arlr is required to maintain lipid homeostasis by downregulating lipolytic genes during aging

Xiaowei Sun, Jie Shen, Norbert Perrimon, Xue Kong and Dan Wang ()
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Xiaowei Sun: China Agricultural University
Jie Shen: China Agricultural University
Norbert Perrimon: Harvard Medical School
Xue Kong: China Agricultural University
Dan Wang: China Agricultural University

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract While disorders in lipid metabolism have been associated with aging and age-related diseases, how lipid metabolism is regulated during aging is poorly understood. Here, we characterize the Drosophila endoribonuclease CG2145, an ortholog of mammalian EndoU that we named Age-related lipid regulator (Arlr), as a regulator of lipid homeostasis during aging. In adult adipose tissues, Arlr is necessary for maintenance of lipid storage in lipid droplets (LDs) as flies age, a phenotype that can be rescued by either high-fat or high-glucose diet. Interestingly, RNA-seq of arlr mutant adipose tissues and RIP-seq suggest that Arlr affects lipid metabolism through the degradation of the mRNAs of lipolysis genes – a model further supported by the observation that knockdown of Lsd-1, regucalcin, yip2 or CG5162, which encode genes involved in lipolysis, rescue the LD defects of arlr mutants. In addition, we characterize DendoU as a functional paralog of Arlr and show that human ENDOU can rescue arlr mutants. Altogether, our study reveals a role of ENDOU-like endonucleases as negative regulator of lipolysis.

Date: 2023
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DOI: 10.1038/s41467-023-42042-7

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