Autophagy As a Modulator of Cell Death Machinery

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2020 Jul 10

PMID 32641772

Citations 79

Authors

Masayuki Noguchi

Noriyuki Hirata

Tsutomu Tanaka

Futoshi Suizu

Hiroshi Nakajima

John A Chiorini

Affiliations

Soon will be listed here.

Abstract

The balance between cell death and survival is a critical parameter in the regulation of cells and the maintenance of homeostasis in vivo. Three major mechanisms for cell death have been identified in mammalian cells: apoptosis (type I), autophagic cell death (type II), and necrosis (type III). These three mechanisms have been suggested to engage in cross talk with each other. Among them, autophagy was originally characterized as a cell survival mechanism for amino acid recycling during starvation. Whether autophagy functions primarily in cell survival or cell death is a critical question yet to be answered. Here, we present a comprehensive review of the cell death-related events that take place during autophagy and their underlying mechanisms in cancer and autoimmune disease development.

Citing Articles

Comparative and Functional Analysis of Exosomal microRNAs During Semelparous Reproduction in Ayu Fish ().

Pan Y, Meng L, Yoshida K, Qiu L, Ito T, Yonezawa R J Extracell Biol. 2025; 4(3):e70038.

PMID: 40066203 PMC: 11891394. DOI: 10.1002/jex2.70038.

Investigation of Non-Coding RNA-Related Autophagy Alterations in Drug-Resistant Multiple Myeloma Plasma Cells.

Sarafraznia L, Tahan Nejad Asadi Z, Dayer D, Jalalifar M, Ghanatir N Iran J Pathol. 2025; 19(4):422-430.

PMID: 40034935 PMC: 11872035. DOI: 10.30699/ijp.2024.2022061.3256.

Biotin Induces Inactive Chromosome X Reactivation and Corrects Physiopathological Alterations in Beta-Propeller-Protein-Associated Neurodegeneration.

Reche-Lopez D, Romero-Gonzalez A, Alvarez-Cordoba M, Suarez-Carrillo A, Cilleros-Holgado P, Pinero-Perez R Int J Mol Sci. 2025; 26(3).

PMID: 39941083 PMC: 11818482. DOI: 10.3390/ijms26031315.

Gboxin Induced Apoptosis and Ferroptosis of Cervical Cancer Cells by Promoting Autophagy-Mediated Inhibition of Nrf2 Signaling Under Low-Glucose Conditions.

Liu W, Lu J, Li J, Wang L, Chen Y, Wu Y Int J Mol Sci. 2025; 26(2.

PMID: 39859216 PMC: 11765388. DOI: 10.3390/ijms26020502.

GABA(A) Receptor Activation Drives GABARAP-Nix Mediated Autophagy to Radiation-Sensitize Primary and Brain-Metastatic Lung Adenocarcinoma Tumors.

Bhattacharya D, Barrile R, Toukam D, Gawali V, Kallay L, Ahmed T Cancers (Basel). 2024; 16(18.

PMID: 39335139 PMC: 11430345. DOI: 10.3390/cancers16183167.

References

He C, Klionsky D . Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet. 2009; 43:67-93. PMC: 2831538. DOI: 10.1146/annurev-genet-102808-114910. View

Amaravadi R, Kimmelman A, Debnath J . Targeting Autophagy in Cancer: Recent Advances and Future Directions. Cancer Discov. 2019; 9(9):1167-1181. PMC: 7306856. DOI: 10.1158/2159-8290.CD-19-0292. View

Kaeberlein M, Powers 3rd R, Steffen K, Westman E, Hu D, Dang N . Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science. 2005; 310(5751):1193-6. DOI: 10.1126/science.1115535. View

Du Toit A . Protein degradation: An alternative route for mitochondrial quality control. Nat Rev Mol Cell Biol. 2014; 15(3):150-1. DOI: 10.1038/nrm3755. View

Noguchi M, Hirata N, Suizu F . The links between AKT and two intracellular proteolytic cascades: ubiquitination and autophagy. Biochim Biophys Acta. 2014; 1846(2):342-52. DOI: 10.1016/j.bbcan.2014.07.013. View

Nagelkerke A, Sieuwerts A, Bussink J, Sweep F, Look M, Foekens J . LAMP3 is involved in tamoxifen resistance in breast cancer cells through the modulation of autophagy. Endocr Relat Cancer. 2014; 21(1):101-12. DOI: 10.1530/ERC-13-0183. View

Noguchi M, Ropars V, Roumestand C, Suizu F . Proto-oncogene TCL1: more than just a coactivator for Akt. FASEB J. 2007; 21(10):2273-84. DOI: 10.1096/fj.06-7684com. View

Gomez-Sintes R, Ledesma M, Boya P . Lysosomal cell death mechanisms in aging. Ageing Res Rev. 2016; 32:150-168. DOI: 10.1016/j.arr.2016.02.009. View

Dorner T, Furie R . Novel paradigms in systemic lupus erythematosus. Lancet. 2019; 393(10188):2344-2358. DOI: 10.1016/S0140-6736(19)30546-X. View

10.

Kaushik S, Cuervo A . Chaperone-mediated autophagy: a unique way to enter the lysosome world. Trends Cell Biol. 2012; 22(8):407-17. PMC: 3408550. DOI: 10.1016/j.tcb.2012.05.006. View

11.

Pedersen N, Raiborg C, Brech A, Skarpen E, Roxrud I, Platta H . The PtdIns3P-binding protein Phafin 2 mediates epidermal growth factor receptor degradation by promoting endosome fusion. Traffic. 2012; 13(11):1547-63. DOI: 10.1111/j.1600-0854.2012.01400.x. View

12.

Ryter S, Mizumura K, Choi A . The impact of autophagy on cell death modalities. Int J Cell Biol. 2014; 2014:502676. PMC: 3932252. DOI: 10.1155/2014/502676. View

13.

Tsokos G . Systemic lupus erythematosus. N Engl J Med. 2011; 365(22):2110-21. DOI: 10.1056/NEJMra1100359. View

14.

Forgac M . Vacuolar ATPases: rotary proton pumps in physiology and pathophysiology. Nat Rev Mol Cell Biol. 2007; 8(11):917-29. DOI: 10.1038/nrm2272. View

15.

Thorburn J, Moore F, Rao A, Barclay W, Thomas L, Grant K . Selective inactivation of a Fas-associated death domain protein (FADD)-dependent apoptosis and autophagy pathway in immortal epithelial cells. Mol Biol Cell. 2005; 16(3):1189-99. PMC: 551484. DOI: 10.1091/mbc.e04-10-0906. View

16.

Amaravadi R, Kimmelman A, White E . Recent insights into the function of autophagy in cancer. Genes Dev. 2016; 30(17):1913-30. PMC: 5066235. DOI: 10.1101/gad.287524.116. View

17.

Brooks Robey R, Hay N . Is Akt the "Warburg kinase"?-Akt-energy metabolism interactions and oncogenesis. Semin Cancer Biol. 2009; 19(1):25-31. PMC: 2814453. DOI: 10.1016/j.semcancer.2008.11.010. View

18.

Poillet-Perez L, White E . Role of tumor and host autophagy in cancer metabolism. Genes Dev. 2019; 33(11-12):610-619. PMC: 6546058. DOI: 10.1101/gad.325514.119. View

19.

Aits S, Jaattela M . Lysosomal cell death at a glance. J Cell Sci. 2013; 126(Pt 9):1905-12. DOI: 10.1242/jcs.091181. View

20.

Kimmelman A . The dynamic nature of autophagy in cancer. Genes Dev. 2011; 25(19):1999-2010. PMC: 3197199. DOI: 10.1101/gad.17558811. View