Autophagy-Mediated Cholesterol Trafficking Controls Steroid Production
| Autor: | Kenneth A. Halberg, Kathrine B. Dall, Alina Malita, Christian F. Christensen, Kim F. Rewitz, Michael J. Texada, Nils J. Færgeman, Stanislav Nagy |
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| Rok vydání: | 2019 |
| Předmět: |
autophagy
steroidogenesis Ecdysone Cell signaling animal structures medicine.medical_treatment Biology General Biochemistry Genetics and Molecular Biology EcR prothoracic gland 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Movement warts Autophagy medicine Animals Drosophila Proteins ecdysone Molecular Biology 030304 developmental biology 0303 health sciences Effector bantam steroid cholesterol Gene Expression Regulation Developmental Nuclear Proteins Tor Cell Biology Cell biology TOR signaling MicroRNAs Steroid hormone Cholesterol chemistry Trans-Activators Drosophila Ecdysone receptor 030217 neurology & neurosurgery Developmental Biology Hormone |
| Zdroj: | Texada, M J, Malita, A, Christensen, C F, Dall, K B, Faergeman, N J, Nagy, S, Halberg, K A & Rewitz, K 2019, ' Autophagy-Mediated Cholesterol Trafficking Controls Steroid Production ', Developmental Cell, vol. 48, no. 5, pp. 659-671.e4 . https://doi.org/10.1016/j.devcel.2019.01.007 |
| ISSN: | 1534-5807 |
| DOI: | 10.1016/j.devcel.2019.01.007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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