The crosstalk between autophagy and apoptosis: where does this lead?
- 2k Downloads
Recent advances in the understanding of the molecular processes contributing to autophagy have provided insight into the relationship between autophagy and apoptosis. In contrast to the concept of “autophagic cell death,” accumulating evidence suggests that autophagy serves a largely cytoprotective role in physiologically relevant conditions. The cytoprotective function of autophagy is mediated in many circumstances by negative modulation of apoptosis. Apoptotic signaling, in turn, serves to inhibit autophagy. While the mechanisms mediating the complex counter-regulation of apoptosis and autophagy are not yet fully understood, important points of crosstalk include the interactions between Beclin-1 and Bcl-2/Bcl-xL and between FADD and Atg5, caspase- and calpain-mediated cleavage of autophagy-related proteins, and autophagic degradation of caspases. Continued investigation of these and other means of crosstalk between apoptosis and autophagy is necessary to elucidate the mechanisms controlling the balance between survival and death both under normal conditions and in diseases including cancer.
Keywordsautophagy apoptosis Beclin-1 lymphocytes
- Anglade, P., Vyas, S., Javoy-Agid, F., Herrero, M.T., Michel, P.P., Marquez, J., Mouatt-Prigent, A., Ruberg, M., Hirsch, E.C., and Agid, Y. (1997). Apoptosis and autophagy in nigral neurons of patients with Parkinson’s disease. Histol Histopathol 12, 25–31.Google Scholar
- Carew, J.S., Nawrocki, S.T., Kahue, C.N., Zhang, H., Yang, C., Chung, L., Houghton, J.A., Huang, P., Giles, F.J., and Cleveland, J. L. (2007). Targeting autophagy augments the anticancer activity of the histone deacetylase inhibitor SAHA to overcome Bcr-Ablmediated drug resistance. Blood 110, 313–322.CrossRefGoogle Scholar
- Kovacs, J.R., Li, C., Yang, Q., Li, G., Garcia, I.G., Ju, S., Roodman, D. G., Windle, J.J., Zhang, X., and Lu, B. (2011). Autophagy promotes T-cell survival through degradation of proteins of the cell death machinery. Cell death and differentiation. 2011 Jun 10. [Epub ahead of print].Google Scholar
- Li, D.D., Wang, L.L., Deng, R., Tang, J., Shen, Y., Guo, J.F., Wang, Y., Xia, L.P., Feng, G.K., Liu, Q.Q., et al. (2009). The pivotal role of c-Jun NH2-terminal kinase-mediated Beclin 1 expression during anticancer agents-induced autophagy in cancer cells. Oncogene 28, 886–898.CrossRefGoogle Scholar
- Liang, X.H., Kleeman, L.K., Jiang, H.H., Gordon, G., Goldman, J.E., Berry, G., Herman, B., and Levine, B. (1998). Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein. J Virol 72, 8586–8596.Google Scholar
- Meléndez, A., Tallóczy, Z., Seaman, M., Eskelinen, E.L., Hall, D.H., and Levine, B. (2003). Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301, 1387–1391.Google Scholar
- Pyo, J.O., Jang, M.H., Kwon, Y.K., Lee, H.J., Jun, J.I., Woo, H.N., Cho, D.H., Choi, B., Lee, H., Kim, J.H., et al. (2005). Essential roles of Atg5 and FADD in autophagic cell death: dissection of autophagic cell death into vacuole formation and cell death. J Biol Chem 280, 20722–20729.CrossRefGoogle Scholar
- Thorburn, J., Moore, F., Rao, A., Barclay, W.W., Thomas, L.R., Grant, K.W., Cramer, S.D., and Thorburn, A. (2005). Selective inactivation of a Fas-associated death domain protein (FADD)-dependent apoptosis and autophagy pathway in immortal epithelial cells. Mol Biol Cell 16, 1189–1199.CrossRefGoogle Scholar
- Wirawan, E., Vande Walle, L., Kersse, K., Cornelis, S., Claerhout, S., Vanoverberghe, I., Roelandt, R., De Rycke, R., Verspurten, J., Declercq, W., et al. (2010). Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria. Cell death & disease 1, e18.CrossRefGoogle Scholar
- Zalckvar, E., Berissi, H., Mizrachy, L., Idelchuk, Y., Koren, I., Eisenstein, M., Sabanay, H., Pinkas-Kramarski, R., and Kimchi, A. (2009b). DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl-XL and induction of autophagy. EMBO Rep 10, 285–292.CrossRefGoogle Scholar