Autophagy-Mediated Cholesterol Trafficking Controls Steroid Production

Developmental Cell
Michael J TexadaKim F Rewitz

Abstract

Steroid hormones are important signaling molecules that regulate growth and drive the development of many cancers. These factors act as long-range signals that systemically regulate the growth of the entire organism, whereas the Hippo/Warts tumor-suppressor pathway acts locally to limit organ growth. We show here that autophagy, a pathway that mediates the degradation of cellular components, also controls steroid production. This process is regulated by Warts (in mammals, LATS1/2) signaling, via its effector microRNA bantam, in response to nutrients. Specifically, autophagy-mediated mobilization and trafficking of the steroid precursor cholesterol from intracellular stores controls the production of the Drosophila steroid ecdysone. Furthermore, we also show that bantam regulates this process via the ecdysone receptor and Tor signaling, identifying pathways through which bantam regulates autophagy and growth. The Warts pathway thus promotes nutrient-dependent systemic growth during development by autophagy-dependent steroid hormone regulation (ASHR). These findings uncover an autophagic trafficking mechanism that regulates steroid production.

Citations

Feb 20, 2020·International Journal of Molecular Sciences·Renald Delanoue, Nuria M Romero
Mar 21, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Do-Hwan LimYoung Sik Lee
May 26, 2020·Cellular and Molecular Life Sciences : CMLS·Takashi KoyamaKim Rewitz
Oct 8, 2020·Genetics·Michael J TexadaKim Rewitz
Oct 22, 2020·Cell Death & Disease·Dongying WangTianmin Xu
Dec 12, 2020·Acta Pharmacologica Sinica·Chan-Juan ZhangLi Qin
Sep 21, 2020·Current Opinion in Insect Science·Xueyang PanMichael B O'Connor
Nov 1, 2020·Current Opinion in Insect Science·Chhavi SoodSarah E Siegrist
May 7, 2021·Genetics·Michael J TexadaKim Rewitz
Jun 27, 2021·Archives of Insect Biochemistry and Physiology·Wentao YeBing Li
Jan 23, 2022·Journal of Physiology and Biochemistry·Haipeng GuoXiaofei Liang

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