Acinus integrates AKT1 and subapoptotic caspase activities to regulate basal autophagy

Journal of Cell Biology

Volumn 207, Issue 2, 2014, Pages 253-268

  Nandi, Nilay ^a   Tyra, Lauren K ^a   Stenesen, Drew ^a   Krämer, Helmut ^a,b  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACINUS; ACTIN; AKT1 PROTEIN; CASPASE; DCP 1 PROTEIN; DROSOPHILA PROTEIN; EPITOPE; HUNTINGTIN; UNCLASSIFIED DRUG; ACINUS PROTEIN, DROSOPHILA; AKT1 PROTEIN, DROSOPHILA; DCP-1 PROTEIN, DROSOPHILA; PROTEIN KINASE B; TRANSCRIPTION FACTOR;

ANIMAL CELL; APOPTOSIS; ARTICLE; AUTOLYSOSOME; AUTOPHAGOSOME; AUTOPHAGY; BASAL AUTOPHAGY; CONTROLLED STUDY; DNA FRAGMENTATION; DROSOPHILA MELANOGASTER; GENE SILENCING; GENOTYPE; LIFESPAN; LOSS OF FUNCTION MUTATION; NERVE DEGENERATION; NONHUMAN; NULL ALLELE; NULL CELL; PHOTORECEPTOR; PHOTORECEPTOR CELL; PROTEIN CLEAVAGE; PROTEIN DEGRADATION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN STABILITY; RETINA CONE; STOP CODON; AMINO ACID SEQUENCE; ANIMAL; BINDING SITE; CYTOLOGY; GENE EXPRESSION REGULATION; GENETICS; LONGEVITY; METABOLISM; MOLECULAR GENETICS; MUTATION; NUCLEOTIDE SEQUENCE; PHYSIOLOGY; SEQUENCE ALIGNMENT;

AMINO ACID SEQUENCE; ANIMALS; APOPTOSIS; AUTOPHAGY; BINDING SITES; CASPASES; CONSERVED SEQUENCE; DROSOPHILA MELANOGASTER; DROSOPHILA PROTEINS; GENE EXPRESSION REGULATION; LONGEVITY; MOLECULAR SEQUENCE DATA; MUTATION; PROTEIN STABILITY; PROTO-ONCOGENE PROTEINS C-AKT; SEQUENCE ALIGNMENT; TRANSCRIPTION FACTORS;

EID: 84910654483     PISSN: 00219525     EISSN: 15408140     Source Type: Journal    
DOI: 10.1083/jcb.201404028     Document Type: Article

References (83)

1. Akbar, M.A., C. Tracy, W.H. Kahr, and H. Krämer. 2011. The full-of-bacteria gene is required for phagosome maturation during immune defense in Drosophila. J. Cell Biol. 192:383-390. http://dx.doi.org/10.1083/jcb.201008119
2. Amarneh, B., K.A. Matthews, and R.B. Rawson. 2009. Activation of sterol regulatory element-binding protein by the caspase Drice in Drosophila larvae. J. Biol. Chem. 284:9674-9682. http://dx.doi.org/10.1074/jbc.M900346200
3. Bai, H., P. Kang, A.M. Hernandez, and M. Tatar. 2013. Activin signaling targeted by insulin/dFOXO regulates aging and muscle proteostasis in Drosophila. PLoS Genet. 9:e1003941. http://dx.doi.org/10.1371/journal.pgen.1003941
4. Barth, J.M., J. Szabad, E. Hafen, and K. Köhler. 2011. Autophagy in Drosophila ovaries is induced by starvation and is required for oogenesis. Cell Death Differ. 18:915-924. http://dx.doi.org/10.1038/cdd.2010.157
5. Berry, D.L., and E.H. Baehrecke. 2007. Growth arrest and autophagy are required for salivary gland cell degradation in Drosophila. Cell. 131:1137-1148. http://dx.doi.org/10.1016/j.cell.2007.10.048
6. Betin, V.M., and J.D. Lane. 2009. Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and triggers mitochondrial targeting and apoptosis. J. Cell Sci. 122:2554-2566. http://dx.doi.org/10.1242/jcs.046250
7. Cadwell, K., J.Y. Liu, S.L. Brown, H. Miyoshi, J. Loh, J.K. Lennerz, C. Kishi, W. Kc, J.A. Carrero, S. Hunt, et al. 2008. A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature. 456:259-263. http://dx.doi.org/10.1038/nature07416
8. Campbell, D.S., and H. Okamoto. 2013. Local caspase activation interacts with Slit-Robo signaling to restrict axonal arborization. J. Cell Biol. 203:657- 672. http://dx.doi.org/10.1083/jcb.201303072
9. Costa-Mattioli, M., and L.M. Monteggia. 2013. mTOR complexes in neurodevelopmental and neuropsychiatric disorders. Nat. Neurosci. 16:1537-1543. http://dx.doi.org/10.1038/nn.3546
10. Demontis, F., and N. Perrimon. 2010. FOXO/4E-BP signaling in Drosophila muscles regulates organism-wide proteostasis during aging. Cell. 143:813- 825. http://dx.doi.org/10.1016/j.cell.2010.10.007
11. Denton, D., B. Shravage, R. Simin, K. Mills, D.L. Berry, E.H. Baehrecke, and S. Kumar. 2009. Autophagy, not apoptosis, is essential for midgut cell death in Drosophila. Curr. Biol. 19:1741-1746. http://dx.doi.org/10.1016/j.cub.2009.08.042
12. Efeyan, A., R. Zoncu, S. Chang, I. Gumper, H. Snitkin, R.L. Wolfson, O. Kirak, D.D. Sabatini, and D.M. Sabatini. 2013. Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival. Nature. 493:679-683. http://dx.doi.org/10.1038/nature11745
13. Faleiro, L., and Y. Lazebnik. 2000. Caspases disrupt the nuclear-cytoplasmic barrier. J. Cell Biol. 151:951-960. http://dx.doi.org/10.1083/jcb.151.5.951
14. Ferdous, A., P.K. Battiprolu, Y.G. Ni, B.A. Rothermel, and J.A. Hill. 2010. FoxO, autophagy, and cardiac remodeling. J. Cardiovasc. Transl. Res. 3:355-364. http://dx.doi.org/10.1007/s12265-010-9200-z
15. Füllgrabe, J., D.J. Klionsky, and B. Joseph. 2014. The return of the nucleus: transcriptional and epigenetic control of autophagy. Nat. Rev. Mol. Cell Biol. 15:65-74. http://dx.doi.org/10.1038/nrm3716
16. Groth, A.C., M. Fish, R. Nusse, and M.P. Calos. 2004. Construction of transgenic Drosophila by using the site-specific integrase from phage phiC31. Genetics. 166:1775-1782. http://dx.doi.org/10.1534/genetics.166.4.1775
17. Haberman, A.S., M.A. Akbar, S. Ray, and H. Krämer. 2010. Drosophila acinus encodes a novel regulator of endocytic and autophagic trafficking. Development. 137:2157-2166. http://dx.doi.org/10.1242/dev.044230
18. Hampe, J., A. Franke, P. Rosenstiel, A. Till, M. Teuber, K. Huse, M. Albrecht, G. Mayr, F.M. De La Vega, J. Briggs, et al. 2007. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat. Genet. 39:207-211. http://dx.doi.org/10.1038/ng1954
19. Hara, T., K. Nakamura, M. Matsui, A. Yamamoto, Y. Nakahara, R. Suzuki-Migishima, M. Yokoyama, K. Mishima, I. Saito, H. Okano, and N. Mizushima. 2006. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature. 441:885-889. http://dx.doi.org/10.1038/nature04724
20. Hayashi, R., D. Handler, D. Ish-Horowicz, and J. Brennecke. 2014. The exon junction complex is required for definition and excision of neighboring introns in Drosophila. Genes Dev. 28:1772-1785. http://dx.doi.org/10.1101/gad.245738.114
21. Hu, Y., J. Yao, Z. Liu, X. Liu, H. Fu, and K. Ye. 2005. Akt phosphorylates acinus and inhibits its proteolytic cleavage, preventing chromatin condensation. EMBO J. 24:3543-3554. http://dx.doi.org/10.1038/sj.emboj.7600823
22. Huang, W.C., and C.C. Chen. 2005. Akt phosphorylation of p300 at Ser-1834 is essential for its histone acetyltransferase and transcriptional activity. Mol. Cell. Biol. 25:6592-6602. http://dx.doi.org/10.1128/MCB.25.15.6592-6602.2005
23. Jang, S.W., S.J. Yang, A. Ehlén, S. Dong, H. Khoury, J. Chen, J.L. Persson, and K. Ye. 2008. Serine/arginine protein-specific kinase 2 promotes leukemia cell proliferation by phosphorylating acinus and regulating cyclin A1. Cancer Res. 68:4559-4570. http://dx.doi.org/10.1158/0008-5472.CAN-08-0021
24. Jewell, J.L., R.C. Russell, and K.L. Guan. 2013. Amino acid signalling upstream of mTOR. Nat. Rev. Mol. Cell Biol. 14:133-139. http://dx.doi.org/10.1038/nrm3522
25. Joselin, A.P., K. Schulze-Osthoff, and C. Schwerk. 2006. Loss of Acinus inhibits oligonucleosomal DNA fragmentation but not chromatin condensation during apoptosis. J. Biol. Chem. 281:12475-12484. http://dx.doi.org/10.1074/jbc.M509859200
26. Juhász, G., and T.P. Neufeld. 2008. Drosophila Atg7: required for stress resistance, longevity and neuronal homeostasis, but not for metamorphosis. Autophagy. 4:357-358. http://dx.doi.org/10.4161/auto.5572
27. Juhász, G., J.H. Hill, Y. Yan, M. Sass, E.H. Baehrecke, J.M. Backer, and T.P. Neufeld. 2008. The class III PI(3)K Vps34 promotes autophagy and endocytosis but not TOR signaling in Drosophila. J. Cell Biol. 181:655- 666. http://dx.doi.org/10.1083/jcb.200712051
28. Kang, C., Y.J. You, and L. Avery. 2007. Dual roles of autophagy in the survival of Caenorhabditis elegans during starvation. Genes Dev. 21:2161-2171. http://dx.doi.org/10.1101/gad.1573107
29. Klionsky, D.J., and Y. Ohsumi. 1999. Vacuolar import of proteins and organelles from the cytoplasm. Annu. Rev. Cell Dev. Biol. 15:1-32. http://dx.doi.org/10.1146/annurev.cellbio.15.1.1
30. Komatsu, M., S. Waguri, T. Chiba, S. Murata, J. Iwata, I. Tanida, T. Ueno, M. Koike, Y. Uchiyama, E. Kominami, and K. Tanaka. 2006. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature. 441:880-884. http://dx.doi.org/10.1038/nature04723
31. Kroemer, G., G. Mariño, and B. Levine. 2010. Autophagy and the integrated stress response. Mol. Cell. 40:280-293. http://dx.doi.org/10.1016/j.molcel.2010.09.023
32. la Cour, T., L. Kiemer, A. Mølgaard, R. Gupta, K. Skriver, and S. Brunak. 2004. Analysis and prediction of leucine-rich nuclear export signals. Protein Eng. Des. Sel. 17:527-536. http://dx.doi.org/10.1093/protein/gzh062
33. Laplante, M., and D.M. Sabatini. 2012. mTOR signaling in growth control and disease. Cell. 149:274-293. http://dx.doi.org/10.1016/j.cell.2012.03.017
34. Laundrie, B., J.S. Peterson, J.S. Baum, J.C. Chang, D. Fileppo, S.R. Thompson, and K. McCall. 2003. Germline cell death is inhibited by P-element insertions disrupting the dcp-1/pita nested gene pair in Drosophila. Genetics. 165:1881-1888.
35. Liang, X.H., S. Jackson, M. Seaman, K. Brown, B. Kempkes, H. Hibshoosh, and B. Levine. 1999. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature. 402:672-676. http://dx.doi.org/10.1038/45257
36. Liu, Y., S. Shoji-Kawata, R.M. Sumpter Jr., Y. Wei, V. Ginet, L. Zhang, B. Posner, K.A. Tran, D.R. Green, R.J. Xavier, et al. 2013. Autosis is a Na+,K+-ATPase-regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia-ischemia. Proc. Natl. Acad. Sci. USA. 110:20364-20371. http://dx.doi.org/10.1073/pnas.1319661110
37. Lo Ré, A.E., M.G. Fernández-Barrena, L.L. Almada, L.D. Mills, S.F. Elsawa, G. Lund, A. Ropolo, M.I. Molejon, M.I. Vaccaro, and M.E. Fernandez-Zapico. 2012. Novel AKT1-GLI3-VMP1 pathway mediates KRAS oncogeneinduced autophagy in cancer cells. J. Biol. Chem. 287:25325-25334. http://dx.doi.org/10.1074/jbc.M112.370809
38. Luo, S., and D.C. Rubinsztein. 2010. Apoptosis blocks Beclin 1-dependent autophagosome synthesis: an effect rescued by Bcl-xL. Cell Death Differ. 17:268-277. http://dx.doi.org/10.1038/cdd.2009.121
39. Malone, C.D., C. Mestdagh, J. Akhtar, N. Kreim, P. Deinhard, R. Sachidanandam, J. Treisman, and J.Y. Roignant. 2014. The exon junction complex controls transposable element activity by ensuring faithful splicing of the piwi transcript. Genes Dev. 28:1786-1799. http://dx.doi.org/10.1101/gad.245829.114
40. Mariño, G., M. Niso-Santano, E.H. Baehrecke, and G. Kroemer. 2014. Selfconsumption: the interplay of autophagy and apoptosis. Nat. Rev. Mol. Cell Biol. 15:81-94. http://dx.doi.org/10.1038/nrm3735
41. Martelli, A.M., G. Tabellini, D. Bressanin, A. Ognibene, K. Goto, L. Cocco, and C. Evangelisti. 2012. The emerging multiple roles of nuclear Akt. Biochim. Biophys. Acta. 1823:2168-2178. http://dx.doi.org/10.1016/j.bbamcr.2012.08.017
42. Meléndez, A., Z. Tallóczy, M. Seaman, E.L. Eskelinen, D.H. Hall, and B. Levine. 2003. Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science. 301:1387-1391. http://dx.doi.org/10.1126/science.1087782
43. Mizushima, N., B. Levine, A.M. Cuervo, and D.J. Klionsky. 2008. Autophagy fights disease through cellular self-digestion. Nature. 451:1069-1075. http://dx.doi.org/10.1038/nature06639
44. Mizushima, N., T. Yoshimori, and Y. Ohsumi. 2011. The role of Atg proteins in autophagosome formation. Annu. Rev. Cell Dev. Biol. 27:107-132. http://dx.doi.org/10.1146/annurev-cellbio-092910-154005
45. Murachelli, A.G., J. Ebert, C. Basquin, H. Le Hir, and E. Conti. 2012. The structure of the ASAP core complex reveals the existence of a Pinin-containing PSAP complex. Nat. Struct. Mol. Biol. 19:378-386. http://dx.doi.org/10.1038/nsmb.2242
46. Murthy, A., Y. Li, I. Peng, M. Reichelt, A.K. Katakam, R. Noubade, M. Roose-Girma, J. DeVoss, L. Diehl, R.R. Graham, and M. van Lookeren Campagne. 2014. A Crohn's disease variant in Atg16l1 enhances its degradation by caspase 3. Nature. 506:456-462. http://dx.doi.org/10.1038/nature13044
47. Nagy, P., M. Kárpáti, A. Varga, K. Pircs, Z. Venkei, S. Takáts, K. Varga, B. Erdi, K. Hegedus, and G. Juhász. 2014. Atg17/FIP200 localizes to perilysosomal Ref(2)P aggregates and promotes autophagy by activation of Atg1 in Drosophila. Autophagy. 10:453-467. http://dx.doi.org/10.4161/auto.27442
48. Nakai, A., O. Yamaguchi, T. Takeda, Y. Higuchi, S. Hikoso, M. Taniike, S. Omiya, I. Mizote, Y. Matsumura, M. Asahi, et al. 2007. The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nat. Med. 13:619-624. http://dx.doi.org/10.1038/nm1574
49. Neufeld, T.P. 2010. TOR-dependent control of autophagy: biting the hand that feeds. Curr. Opin. Cell Biol. 22:157-168. http://dx.doi.org/10.1016/j.ceb.2009.11.005
50. Orvedahl, A., R. Sumpter Jr., G. Xiao, A. Ng, Z. Zou, Y. Tang, M. Narimatsu, C. Gilpin, Q. Sun, M. Roth, et al. 2011. Image-based genome-wide siRNA screen identifies selective autophagy factors. Nature. 480:113-117. http://dx.doi.org/10.1038/nature10546
51. Park, H.S., Y. Yun, C.S. Kim, K.H. Yang, M. Jeong, S.K. Ahn, Y.W. Jin, and S.Y. Nam. 2009. A critical role for AKT activation in protecting cells from ionizing radiation-induced apoptosis and the regulation of acinus gene expression. Eur. J. Cell Biol. 88:563-575. http://dx.doi.org/10.1016/j.ejcb.2009.05.004
52. Patwa, T.H., Y. Wang, F.R. Miller, S. Goodison, S. Pennathur, T.J. Barder, and D.M. Lubman. 2008. A novel phosphoprotein analysis scheme for assessing changes in premalignant and malignant breast cell lines using 2D liquid separations, protein microarrays and tandem mass spectrometry. Proteomics Clin. Appl. 3:51-66. http://dx.doi.org/10.1002/prca.200800097
53. Pulipparacharuvil, S., M.A. Akbar, S. Ray, E.A. Sevrioukov, A.S. Haberman, J. Rohrer, and H. Krämer. 2005. Drosophila Vps16A is required for trafficking to lysosomes and biogenesis of pigment granules. J. Cell Sci. 118:3663-3673. http://dx.doi.org/10.1242/jcs.02502
54. Rigou, P., V. Piddubnyak, A. Faye, J.C. Rain, L. Michel, F. Calvo, and J.L. Poyet. 2009. The antiapoptotic protein AAC-11 interacts with and regulates Acinus-mediated DNA fragmentation. EMBO J. 28:1576-1588. http://dx.doi.org/10.1038/emboj.2009.106
55. Rudrapatna, V.A., E. Bangi, and R.L. Cagan. 2013. Caspase signalling in the absence of apoptosis drives Jnk-dependent invasion. EMBO Rep. 14:172- 177. http://dx.doi.org/10.1038/embor.2012.217
56. Rusten, T.E., K. Lindmo, G. Juhász, M. Sass, P.O. Seglen, A. Brech, and H. Stenmark. 2004. Programmed autophagy in the Drosophila fat body is induced by ecdysone through regulation of the PI3K pathway. Dev. Cell. 7:179-192. http://dx.doi.org/10.1016/j.devcel.2004.07.005
57. Sahara, S., M. Aoto, Y. Eguchi, N. Imamoto, Y. Yoneda, and Y. Tsujimoto. 1999. Acinus is a caspase-3-activated protein required for apoptotic chromatin condensation. Nature. 401:168-173. http://dx.doi.org/10.1038/43678
58. Sarkar, S., B. Ravikumar, R.A. Floto, and D.C. Rubinsztein. 2009. Rapamycin and mTOR-independent autophagy inducers ameliorate toxicity of polyglutamine-expanded huntingtin and related proteinopathies. Cell Death Differ. 16:46-56. http://dx.doi.org/10.1038/cdd.2008.110
59. Scherzinger, E., R. Lurz, M. Turmaine, L. Mangiarini, B. Hollenbach, R. Hasenbank, G.P. Bates, S.W. Davies, H. Lehrach, and E.E. Wanker. 1997. Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Cell. 90:549-558. http://dx.doi.org/10.1016/S0092-8674(00)80514-0
60. Schwerk, C., J. Prasad, K. Degenhardt, H. Erdjument-Bromage, E. White, P. Tempst, V.J. Kidd, J.L. Manley, J.M. Lahti, and D. Reinberg. 2003. ASAP, a novel protein complex involved in RNA processing and apoptosis. Mol. Cell. Biol. 23:2981-2990. http://dx.doi.org/10.1128/MCB.23.8.2981-2990.2003
61. Scott, R.C., O. Schuldiner, and T.P. Neufeld. 2004. Role and regulation of starvation-induced autophagy in the Drosophila fat body. Dev. Cell. 7:167-178. http://dx.doi.org/10.1016/j.devcel.2004.07.009
62. Scott, R.C., G. Juhász, and T.P. Neufeld. 2007. Direct induction of autophagy by Atg1 inhibits cell growth and induces apoptotic cell death. Curr. Biol. 17:1-11. http://dx.doi.org/10.1016/j.cub.2006.10.053
63. Settembre, C., R. Zoncu, D.L. Medina, F. Vetrini, S. Erdin, S. Erdin, T. Huynh, M. Ferron, G. Karsenty, M.C. Vellard, et al. 2012. A lysosometo-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. EMBO J. 31:1095-1108. http://dx.doi.org/10.1038/emboj.2012.32
64. Shoji-Kawata, S., R. Sumpter, M. Leveno, G.R. Campbell, Z. Zou, L. Kinch, A.D. Wilkins, Q. Sun, K. Pallauf, D. MacDuff, et al. 2013. Identification of a candidate therapeutic autophagy-inducing peptide. Nature. 494:201- 206. http://dx.doi.org/10.1038/nature11866
65. Shu, Y., T. Iijima, W. Sun, J. Kano, T. Ishiyama, C. Okubo, Y. Anami, R. Tanaka, S. Fukai, and M. Noguchi. 2006. The ACIN1 gene is hypermethylated in early stage lung adenocarcinoma. J. Thorac. Oncol. 1:160-167. http://dx.doi.org/10.1097/01243894-200602000-00010
66. Simonsen, A., R.C. Cumming, and K.D. Finley. 2007. Linking lysosomal trafficking defects with changes in aging and stress response in Drosophila. Autophagy. 3:499-501. http://dx.doi.org/10.4161/auto.4604
67. Simonsen, A., R.C. Cumming, A. Brech, P. Isakson, D.R. Schubert, and K.D. Finley. 2008. Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila. Autophagy. 4:176-184. http://dx.doi.org/10.4161/auto.5269
68. Singh, G., A. Kucukural, C. Cenik, J.D. Leszyk, S.A. Shaffer, Z. Weng, and M.J. Moore. 2012. The cellular EJC interactome reveals higher-order mRNP structure and an EJC-SR protein nexus. Cell. 151:750-764. http://dx.doi.org/10.1016/j.cell.2012.10.007
69. Singh, K.K., S. Erkelenz, S. Rattay, A.K. Dehof, A. Hildebrandt, K. Schulze-Osthoff, H. Schaal, and C. Schwerk. 2010. Human SAP18 mediates assembly of a splicing regulatory multiprotein complex via its ubiquitinlike fold. RNA. 16:2442-2454. http://dx.doi.org/10.1261/rna.2304410
70. Spencer, B., R. Potkar, M. Trejo, E. Rockenstein, C. Patrick, R. Gindi, A. Adame, T. Wyss-Coray, and E. Masliah. 2009. Beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative pathology in α-synuclein models of Parkinson's and Lewy body diseases. J. Neurosci. 29:13578- 13588. http://dx.doi.org/10.1523/JNEUROSCI.4390-09.2009
71. Steffan, J.S., L. Bodai, J. Pallos, M. Poelman, A. McCampbell, B.L. Apostol, A. Kazantsev, E. Schmidt, Y.Z. Zhu, M. Greenwald, et al. 2001. Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature. 413:739-743. http://dx.doi.org/10.1038/35099568
72. Stenesen, D., J.M. Suh, J. Seo, K. Yu, K.S. Lee, J.S. Kim, K.J. Min, and J.M. Graff. 2013. Adenosine nucleotide biosynthesis and AMPK regulate adult life span and mediate the longevity benefit of caloric restriction in flies. Cell Metab. 17:101-112. http://dx.doi.org/10.1016/j.cmet.2012.12.006
73. Tange, T.O., T. Shibuya, M.S. Jurica, and M.J. Moore. 2005. Biochemical analysis of the EJC reveals two new factors and a stable tetrameric protein core. RNA. 11:1869-1883. http://dx.doi.org/10.1261/rna.2155905
74. Vellai, T., K. Takács-Vellai, M. Sass, and D.J. Klionsky. 2009. The regulation of aging: does autophagy underlie longevity? Trends Cell Biol. 19:487-494. http://dx.doi.org/10.1016/j.tcb.2009.07.007
75. Venken, K.J., Y. He, R.A. Hoskins, and H.J. Bellen. 2006. P[acman]: a BAC transgenic platform for targeted insertion of large DNA fragments in D. melanogaster. Science. 314:1747-1751. http://dx.doi.org/10.1126/science.1134426
76. Wang, R.C., Y. Wei, Z. An, Z. Zou, G. Xiao, G. Bhagat, M. White, J. Reichelt, and B. Levine. 2012. Akt-mediated regulation of autophagy and tumorigenesis through Beclin 1 phosphorylation. Science. 338:956-959. http://dx.doi.org/10.1126/science.1225967
77. White, E. 2012. Deconvoluting the context-dependent role for autophagy in cancer. Nat. Rev. Cancer. 12:401-410. http://dx.doi.org/10.1038/nrc3262
78. Williamson, W.R., D. Wang, A.S. Haberman, and P.R. Hiesinger. 2010. A dual function of V0-ATPase a1 provides an endolysosomal degradation mechanism in Drosophila melanogaster photoreceptors. J. Cell Biol. 189:885- 899. http://dx.doi.org/10.1083/jcb.201003062
79. Wirawan, E., L. Vande Walle, K. Kersse, S. Cornelis, S. Claerhout, I. Vanoverberghe, R. Roelandt, R. De Rycke, J. Verspurten, W. Declercq, 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 Dis. 1:e18. http://dx.doi.org/10.1038/cddis.2009.16
80. Wolff, T. 2011. Preparation of Drosophila eye specimens for scanning electron microscopy. Cold Spring Harb. Protoc. 2011:1383-1385.
81. Wolff, T., and D.F. Ready. 1993. Pattern formation in the Drosophila retina. In The Development of Drosophila melanogaster. M. Bate and A. Martinez-Arias, editors. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. 1277-1325.
82. Yan, L., and R.F. Lamb. 2012. Amino acid sensing and regulation of mTORC1. Semin. Cell Dev. Biol. 23:621-625. http://dx.doi.org/10.1016/j.semcdb.2012.02.001
83. Yang, Z., and D.J. Klionsky. 2010. Mammalian autophagy: core molecular machinery and signaling regulation. Curr. Opin. Cell Biol. 22:124-131. http://dx.doi.org/10.1016/j.ceb.2009.11.014