Autophagy-Mediated Cholesterol Trafficking Controls Steroid Production

Michael J. Texada, Alina Malita, Christian F. Christensen, Kathrine B. Dall, Nils J. Faergeman, Stanislav Nagy, Kenneth A. Halberg, Kim Rewitz*

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftDevelopmental Cell
Vol/bind48
Udgave nummer5
Sider (fra-til)659-671.e4
ISSN1534-5807
DOI
StatusUdgivet - 11. mar. 2019

Fingeraftryk

Steroids
Cholesterol
Steroid hormones
Nutrients
Growth and Development
Ecdysone
Growth
Inventory control
Mammals
Hormones
Food
MicroRNAs
Tumors
Neoplasms
Degradation
Molecules

Citer dette

Texada, Michael J. ; Malita, Alina ; Christensen, Christian F. ; Dall, Kathrine B. ; Faergeman, Nils J. ; Nagy, Stanislav ; Halberg, Kenneth A. ; Rewitz, Kim. / Autophagy-Mediated Cholesterol Trafficking Controls Steroid Production. I: Developmental Cell. 2019 ; Bind 48, Nr. 5. s. 659-671.e4.
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title = "Autophagy-Mediated Cholesterol Trafficking Controls Steroid Production",
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.",
keywords = "autophagy, bantam, cholesterol, Drosophila, ecdysone, EcR, prothoracic gland, steroid, steroidogenesis, Tor, warts",
author = "Texada, {Michael J.} and Alina Malita and Christensen, {Christian F.} and Dall, {Kathrine B.} and Faergeman, {Nils J.} and Stanislav Nagy and Halberg, {Kenneth A.} and Kim Rewitz",
year = "2019",
month = "3",
day = "11",
doi = "10.1016/j.devcel.2019.01.007",
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Texada, MJ, Malita, A, Christensen, CF, Dall, KB, Faergeman, NJ, Nagy, S, Halberg, KA & Rewitz, K 2019, 'Autophagy-Mediated Cholesterol Trafficking Controls Steroid Production', Developmental Cell, bind 48, nr. 5, s. 659-671.e4. https://doi.org/10.1016/j.devcel.2019.01.007

Autophagy-Mediated Cholesterol Trafficking Controls Steroid Production. / Texada, Michael J.; Malita, Alina; Christensen, Christian F.; Dall, Kathrine B.; Faergeman, Nils J.; Nagy, Stanislav; Halberg, Kenneth A.; Rewitz, Kim.

I: Developmental Cell, Bind 48, Nr. 5, 11.03.2019, s. 659-671.e4.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Autophagy-Mediated Cholesterol Trafficking Controls Steroid Production

AU - Texada, Michael J.

AU - Malita, Alina

AU - Christensen, Christian F.

AU - Dall, Kathrine B.

AU - Faergeman, Nils J.

AU - Nagy, Stanislav

AU - Halberg, Kenneth A.

AU - Rewitz, Kim

PY - 2019/3/11

Y1 - 2019/3/11

N2 - 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.

AB - 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.

KW - autophagy

KW - bantam

KW - cholesterol

KW - Drosophila

KW - ecdysone

KW - EcR

KW - prothoracic gland

KW - steroid

KW - steroidogenesis

KW - Tor

KW - warts

U2 - 10.1016/j.devcel.2019.01.007

DO - 10.1016/j.devcel.2019.01.007

M3 - Journal article

VL - 48

SP - 659-671.e4

JO - Developmental Cell

JF - Developmental Cell

SN - 1534-5807

IS - 5

ER -