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

Author

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  • Xiaowei Sun

    (China Agricultural University)

  • Jie Shen

    (China Agricultural University)

  • Norbert Perrimon

    (Harvard Medical School
    Howard Hughes Medical Institute)

  • Xue Kong

    (China Agricultural University)

  • Dan Wang

    (China Agricultural University)

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.

Suggested Citation

  • Xiaowei Sun & Jie Shen & Norbert Perrimon & Xue Kong & Dan Wang, 2023. "The endoribonuclease Arlr is required to maintain lipid homeostasis by downregulating lipolytic genes during aging," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42042-7
    DOI: 10.1038/s41467-023-42042-7
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    References listed on IDEAS

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    1. Sihui Wang & Fatima-Zahra Idrissi & Martin Hermansson & Alexandra Grippa & Christer S. Ejsing & Pedro Carvalho, 2018. "Seipin and the membrane-shaping protein Pex30 cooperate in organelle budding from the endoplasmic reticulum," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    2. Rajat Singh & Susmita Kaushik & Yongjun Wang & Youqing Xiang & Inna Novak & Masaaki Komatsu & Keiji Tanaka & Ana Maria Cuervo & Mark J. Czaja, 2009. "Autophagy regulates lipid metabolism," Nature, Nature, vol. 458(7242), pages 1131-1135, April.
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