Emerging Role of the Hippo Pathway in Autophagy

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2020 Oct 21

PMID 33082313

Citations 30

Authors

Dongying Wang

Jiaxing He

Bingyu Huang

Shanshan Liu

Hongming Zhu

Tianmin Xu

Affiliations

Soon will be listed here.

Abstract

Autophagy is a dynamic circulatory system that occurs in all eukaryotic cells. Cytoplasmic material is transported to lysosomes for degradation and recovery through autophagy. This provides energy and macromolecular precursors for cell renewal and homeostasis. The Hippo-YAP pathway has significant biological properties in controlling organ size, tissue homeostasis, and regeneration. Recently, the Hippo-YAP axis has been extensively referred to as the pathophysiological processes regulating autophagy. Understanding the cellular and molecular basis of these processes is crucial for identifying disease pathogenesis and novel therapeutic targets. Here we review recent findings from Drosophila models to organisms. We particularly emphasize the regulation between Hippo core components and autophagy, which is involved in normal cellular regulation and the pathogenesis of human diseases, and its application to disease treatment.

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References

Abada A, Elazar Z . Getting ready for building: signaling and autophagosome biogenesis. EMBO Rep. 2014; 15(8):839-52. PMC: 4197041. DOI: 10.15252/embr.201439076. View

Kim T, Hwang D, Lee D, Kim J, Kim S, Lim D . MRTF potentiates TEAD-YAP transcriptional activity causing metastasis. EMBO J. 2016; 36(4):520-535. PMC: 5694947. DOI: 10.15252/embj.201695137. View

Pefani D, Pankova D, Abraham A, Grawenda A, Vlahov N, Scrace S . TGF-β Targets the Hippo Pathway Scaffold RASSF1A to Facilitate YAP/SMAD2 Nuclear Translocation. Mol Cell. 2016; 63(1):156-66. DOI: 10.1016/j.molcel.2016.05.012. View

Lee Y, Noon L, Akat K, Ybanez M, Lee T, Berres M . Autophagy is a gatekeeper of hepatic differentiation and carcinogenesis by controlling the degradation of Yap. Nat Commun. 2018; 9(1):4962. PMC: 6251897. DOI: 10.1038/s41467-018-07338-z. View

Tsukada M, Ohsumi Y . Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett. 1993; 333(1-2):169-74. DOI: 10.1016/0014-5793(93)80398-e. View

Singh S, Vats S, Chia A, Tan T, Deng S, Ong M . Dual role of autophagy in hallmarks of cancer. Oncogene. 2017; 37(9):1142-1158. DOI: 10.1038/s41388-017-0046-6. View

Xiao L, Shi X, Zhang Y, Zhu Y, Zhu L, Tian W . YAP induces cisplatin resistance through activation of autophagy in human ovarian carcinoma cells. Onco Targets Ther. 2016; 9:1105-14. PMC: 4806764. DOI: 10.2147/OTT.S102837. View

Udan R, Kango-Singh M, Nolo R, Tao C, Halder G . Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathway. Nat Cell Biol. 2003; 5(10):914-20. DOI: 10.1038/ncb1050. View

Wang S, Zhao Z, Feng X, Cheng Z, Xiong Z, Wang T . Melatonin activates Parkin translocation and rescues the impaired mitophagy activity of diabetic cardiomyopathy through Mst1 inhibition. J Cell Mol Med. 2018; 22(10):5132-5144. PMC: 6156356. DOI: 10.1111/jcmm.13802. View

10.

Danielsen E, Moeller M, Yamanaka N, Ou Q, Laursen J, Soenderholm C . A Drosophila Genome-Wide Screen Identifies Regulators of Steroid Hormone Production and Developmental Timing. Dev Cell. 2016; 37(6):558-70. PMC: 4918455. DOI: 10.1016/j.devcel.2016.05.015. View

11.

Mulcahy Levy J, Thorburn A . Autophagy in cancer: moving from understanding mechanism to improving therapy responses in patients. Cell Death Differ. 2019; 27(3):843-857. PMC: 7206017. DOI: 10.1038/s41418-019-0474-7. View

12.

Jiang P, Mizushima N . LC3- and p62-based biochemical methods for the analysis of autophagy progression in mammalian cells. Methods. 2014; 75:13-8. DOI: 10.1016/j.ymeth.2014.11.021. View

13.

Lin J, Zhang L, Zhang M, Hu J, Wang T, Duan Y . Mst1 inhibits CMECs autophagy and participates in the development of diabetic coronary microvascular dysfunction. Sci Rep. 2016; 6:34199. PMC: 5040958. DOI: 10.1038/srep34199. View

14.

Chen R, Zhu S, Fan X, Wang H, Lotze M, Zeh 3rd H . High mobility group protein B1 controls liver cancer initiation through yes-associated protein -dependent aerobic glycolysis. Hepatology. 2017; 67(5):1823-1841. PMC: 5906197. DOI: 10.1002/hep.29663. View

15.

Texada M, Malita A, Christensen C, Dall K, Faergeman N, Nagy S . Autophagy-Mediated Cholesterol Trafficking Controls Steroid Production. Dev Cell. 2019; 48(5):659-671.e4. DOI: 10.1016/j.devcel.2019.01.007. View

16.

Rabinowitz J, White E . Autophagy and metabolism. Science. 2010; 330(6009):1344-8. PMC: 3010857. DOI: 10.1126/science.1193497. View

17.

Ktistakis N, Tooze S . Digesting the Expanding Mechanisms of Autophagy. Trends Cell Biol. 2016; 26(8):624-635. DOI: 10.1016/j.tcb.2016.03.006. View

18.

Napoletano F, Occhi S, Calamita P, Volpi V, Blanc E, Charroux B . Polyglutamine Atrophin provokes neurodegeneration in Drosophila by repressing fat. EMBO J. 2011; 30(5):945-58. PMC: 3049215. DOI: 10.1038/emboj.2011.1. View

19.

Chen H, White E . Role of autophagy in cancer prevention. Cancer Prev Res (Phila). 2011; 4(7):973-83. PMC: 3136921. DOI: 10.1158/1940-6207.CAPR-10-0387. View

20.

Yang Z, Klionsky D . Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol. 2009; 22(2):124-31. PMC: 2854249. DOI: 10.1016/j.ceb.2009.11.014. View