» Articles » PMID: 18083103

Growth Arrest and Autophagy Are Required for Salivary Gland Cell Degradation in Drosophila

Overview
Journal Cell
Publisher Cell Press
Specialty Cell Biology
Date 2007 Dec 18
PMID 18083103
Citations 304
Authors
Affiliations
Soon will be listed here.
Abstract

Autophagy is a catabolic process that is negatively regulated by growth and has been implicated in cell death. We find that autophagy is induced following growth arrest and precedes developmental autophagic cell death of Drosophila salivary glands. Maintaining growth by expression of either activated Ras or positive regulators of the class I phosphoinositide 3-kinase (PI3K) pathway inhibits autophagy and blocks salivary gland cell degradation. Developmental degradation of salivary glands is also inhibited in autophagy gene (atg) mutants. Caspases are active in PI3K-expressing and atg mutant salivary glands, and combined inhibition of both autophagy and caspases increases suppression of gland degradation. Further, induction of autophagy is sufficient to induce premature cell death in a caspase-independent manner. Our results provide in vivo evidence that growth arrest, autophagy, and atg genes are required for physiological autophagic cell death and that multiple degradation pathways cooperate in the efficient clearance of cells during development.

Citing Articles

The calcium pump PMCA4b promotes epithelial cell polarization and lumen formation.

Toth S, Kaszas D, Sonyak J, Tokes A, Padanyi R, Papp B Commun Biol. 2025; 8(1):421.

PMID: 40075218 PMC: 11904214. DOI: 10.1038/s42003-025-07814-5.


The pro-fibrotic role of autophagy in renal intrinsic cells: mechanisms and therapeutic potential in chronic kidney disease.

Zhang Y, Zhou X, Huang G, Liao W, Chen X, Ma Y Front Cell Dev Biol. 2024; 12:1499457.

PMID: 39723243 PMC: 11669005. DOI: 10.3389/fcell.2024.1499457.


Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression.

He R, Liu Y, Fu W, He X, Liu S, Xiao D Mol Cancer. 2024; 23(1):267.

PMID: 39614268 PMC: 11606237. DOI: 10.1186/s12943-024-02172-y.


Inhibition of autophagy as a novel treatment for neurofibromatosis type 1 tumors.

Stevens M, Wang Y, Bouley S, Mandigo T, Sharma A, Sengupta S Mol Oncol. 2024; 19(3):825-851.

PMID: 39129390 PMC: 11887668. DOI: 10.1002/1878-0261.13704.


Whole-body replacement of larval myofibers generates permanent adult myofibers in zebrafish.

Kumar U, Fang C, Roan H, Hsu S, Wang C, Chen C EMBO J. 2024; 43(15):3090-3115.

PMID: 38839992 PMC: 11294464. DOI: 10.1038/s44318-024-00136-y.


References
1.
Shimizu S, Kanaseki T, Mizushima N, Mizuta T, Arakawa-Kobayashi S, Thompson C . Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol. 2004; 6(12):1221-8. DOI: 10.1038/ncb1192. View

2.
Klionsky D, Emr S . Autophagy as a regulated pathway of cellular degradation. Science. 2000; 290(5497):1717-21. PMC: 2732363. DOI: 10.1126/science.290.5497.1717. View

3.
Debnath J, Mills K, Collins N, Reginato M, Muthuswamy S, Brugge J . The role of apoptosis in creating and maintaining luminal space within normal and oncogene-expressing mammary acini. Cell. 2002; 111(1):29-40. DOI: 10.1016/s0092-8674(02)01001-2. View

4.
Cantley L, Neel B . New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci U S A. 1999; 96(8):4240-5. PMC: 33561. DOI: 10.1073/pnas.96.8.4240. View

5.
Britton J, Lockwood W, Li L, Cohen S, Edgar B . Drosophila's insulin/PI3-kinase pathway coordinates cellular metabolism with nutritional conditions. Dev Cell. 2002; 2(2):239-49. DOI: 10.1016/s1534-5807(02)00117-x. View