Table 1:
C. elegans autophagy genes
| C. elegans Atg gene | Allele | Yeast/Mammalian ortholog | Phenotype in C. elegans | Reference |
|---|---|---|---|---|
| let-363R | h98 | TOR1,2/mTOR | Let, LL | (Brown et al. 1994; Noda and Ohsumi 1998; Vellai et al. 2003; Jia et al. 2004; Hansen et al. 2007; Hansen et al. 2008) |
| unc-51R | e369 | ATG1/Ulk1/2 | Unc, AbD, Pg, Egl | (Hedgecock et al. 1985; Ogura et al. 1994; Matsuura et al. 1997; Kuroyanagi et al. 1998; Meléndez et al. 2003; Zhang et al. 2009) |
| epg-1R | bp414 | ATG13/Atg13 | Dv, Pg | (Funakoshi et al. 1997; Chan et al. 2009; Tian et al. 2009) |
| bec-1R | ok691 | ATG6,VPS30/beclin 1 | Let, AbD, St, SL, Pg pQ | (Seaman et al. 1997; Kametaka et al. 1998; Kihara et al. 2001; Meléndez et al. 2003; Takacs-Vellai et al. 2005; Jia et al. 2007; Hansen et al. 2008; Zhao et al. 2009; Ruck et al. 2011) |
| let-512/vps-34R | h797 | VPS34/Vps34 | Let, SL, Pg | (Seglen and Gordon 1982; Volinia et al. 1995; Roggo et al. 2002; Zhao et al. 2009; Ruck et al. 2011) |
| ZK930.1R | ok3132 | VPS15/p150 | ND | (Panaretou et al. 1997; Kihara et al. 2001; Kovács et al. 2003) |
| epg-8R | bp251 | ATG14/Atg14L, Barkor | Dv, Pg | (Kihara et al. 2001; Obara et al. 2006; Sun et al. 2008); (Fan et al. 2011; Yang and Zhang 2011) |
| epg-6 | bp242 | -/WIPI4 | Dv, Pg | (Lu et al. 2011) |
| epg-3R | bp405 | -/VMP1 | Dv, Pg | (Tian et al. 2010) |
| epg-4R | bp425 | -/EI24,PIG8 | Dv, Pg | (Tian et al. 2010) |
| atg-3 | bp412 | ATG3/Atg3 | Pg | (Tanida et al. 2002; Zhang et al. 2009) |
| atg-4.1*R | tm3949 | ATG4/Atg4 | Pg | (Kirisako et al. 2000; Tanida et al. 2004; Zhang et al. 2009) |
| atg-4.2*R | tm3948 | ATG4/Atg4 | ND | (Kirisako et al. 2000; Tanida et al. 2004; Zhang et al. 2009) |
| atg-5 | bp545 | ATG5/Atg5 | ND | (Mizushima et al. 1998; Mizushima et al. 2001; Tian et al. 2010) |
| atg7/M7.5R | tm831 | ATG7/Atg7 | AbD, SL, Pg, pQ | (Kim et al. 1999; Tanida et al. 2001; Meléndez et al. 2003) |
| Igg-1R | bp500, tm3489 | ATG8/LC3 | Let, Dv, AbD, SL, Pg | (Kirisako et al. 2000; He et al. 2003; Meléndez et al. 2003); (Zhang et al. 2009; Alberti et al. 2010) |
| Igg-2R | - | ATG8/LC3 | Let, Dv, AbD, SL, Pg | (Kirisako et al. 2000; He et al. 2003; Meléndez et al. 2003; Zhang et al. 2009; Alberti et al. 2010) |
| atg-10R | bp588 | ATG10/Atg10 | ND | (Takahiro Shintani 1999; Mizushima et al. 2002; Meléndez et al. 2003; Tian et al. 2010) |
| Igg-3R | gk1857 | ATG12/Atg12 | SL, Pg | (Mizushima et al. 1998; Meléndez et al. 2003; Hars et al. 2007) |
| atg-16.1*R | - | ATG16/Atg16L1 | ND | (Kuma et al. 2002; Mizushima et al. 2003; Tian et al. 2010) |
| atg-16.2*R | ok3224 | ATG16/Atg16L1 | ND | (Kuma et al. 2002; Mizushima et al. 2003; Tian et al. 2010) |
| atg-2 | bp576 | ATG2/Atg2 | (Shintani 2001; Wang et al. 2001; Lu et al. 2011) | |
| atg-9R | bp564 | ATG9/Atg9 | (Noda et al. 2000; Yamada et al. 2005; Reggiori 2006) | |
| atg-18R | gk378 | ATG18/WIPI1/2 | Let, AbD, Pg, pQ | (Barth 2001; Meléndez et al. 2003; Jia et al. 2007); (Polson et al. 2010; Tian et al. 2010) |
| epg-2 | bp287 | -/- | Pg | (Tian et al. 2010) |
| epg-5R | bp450 | -/ KIAA1632 | Dv, Pg | (Tian et al. 2010) |
| sepa-1 | bp402 | -/- | Pg | (Zhang et al. 2009) |
| T12G3.1 | ok2892 | -/p62(SQSTM1) | (Tian et al. 2010; Lu et al. 2011) |
Let= Lethal; Unc= uncoordinated; Dv = Decreased viability of L1s during starvation; AbD= Abnormal Dauer; St= Sterile; LL= Long lifespan; SL= Short Lifespan; Pg= P granule accumulation; Egl= Egg laying defective; pQ= polyQ expansion susceptibility; ND= Not determined
Paralogs in C. elegans
RNAi clone available
Alberti A, Michelet X, Djeddi A, Legouis R. 2010. The autophagosomal protein LGG-2 acts synergistically with LGG-1 in dauer formation and longevity in C. elegans. Autophagy 6: 622–633.
Barth H, Meiling-Wesse, K., Epple, U. D., and Thumm, M. 2001. Autophagy and the cytoplasm to vacuole targeting pathway both require Aut10p. FEBS letters 508: 23–28.
Brown EJ, Albers MW, Bum Shin T, Ichikawa K, Keith CT, Lane WS, Schreiber SL. 1994. A mammalian protein targeted by Gl-arresting rapamycin–receptor complex. Nature 369: 756–758.
Chan EY, Longatti A, McKnight NC, Tooze SA. 2009. Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-terminal domains using an Atg13-independent mechanism. Molecular and cellular biology 29: 157–171.
Fan W, Nassiri A, Zhong Q. 2011. Autophagosome targeting and membrane curvature sensing by Barkor/Atg14(L). PNAS 108.
Funakoshi T, Matsuura A, Noda T, Ohsumi Y. 1997. Analyses of APG13 gene involved in autophagy in yeast, Saccharomyces cerevisiae. Gene 192: 207–213.
Hansen M, Chandra A, Mitic LL, Onken B, Driscoll M, Kenyon C. 2008. A Role for Autophagy in the Extension of Lifespan by Dietary Restriction in C. elegans. PLoS genetics 4: e24.
Hansen M, Taubert S, Crawford D, Libina N, Lee SJ, Kenyon C. 2007. Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging cell 6: 95–110.
Hars ES, Qi H, Ryazanov AG, Jin S, Cai L, Hu C, Liu LF. 2007. Autophagy regulates ageing in C. elegans. Autophagy 3: 93–95.
He H, Dang Y, Dai F, Guo Z, Wu J, She X, Pei Y, Chen Y, Ling W, Wu C et al. 2003. Post-translational modifications of three members of the human MAP1LC3 family and detection of a novel type of modification for MAP1LC3B. The Journal of biological chemistry 278: 29278–29287.
Hedgecock EM, Culotti JG, Thomson JN, Perkins LA. 1985. Axonal guidance mutants of Caenorhabditis elegans identified by filling sensory neurons with fluorescein dyes. Developmental biology 111: 158–170.
Jia K, Chen D, Riddle DL. 2004. The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span. Development 131: 3897–3906.
Jia K, Hart AC, Levine B. 2007. Autophagy genes protect against disease caused by polyglutamine expansion proteins in Caenorhabditis elegans. Autophagy 3: 21–25.
Kametaka S, Okano T, Ohsumi M, Ohsumi Y. 1998. Apg14p and Apg6/Vps30p form a protein complex essential for autophagy in the yeast, Saccharomyces cerevisiae. The Journal of biological chemistry 273: 22284–22291.
Kihara A, Noda T, Ishihara N, Ohsumi Y. 2001. Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae. The Journal of cell biology 152: 519–530.
Kim J, Dalton VM, Eggerton KP, Scott SV, Klionsky DJ. 1999. Apg7p/Cvt2p is required for the cytoplasm-to-vacuole targeting, macroautophagy, and peroxisome degradation pathways. Molecular biology of the cell 10: 1337–1351.
Kirisako T, Ichimura Y, Okada H, Kabeya Y, Mizushima N, Yoshimori T, Ohsumi M, Takao T, Noda T, Ohsumi Y. 2000. The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway. The Journal of cell biology 151: 263–276.
Kovács AL, Vellai T, Müller F. 2003. Autophagy in Caenorhabditis elegans. In Autophagy, D. Klionsky. 219–225.
Kuma A, Mizushima N, Ishihara N, Ohsumi Y. 2002. Formation of the approximately 350-kDa Apg12-Apg5.Apg16 multimeric complex, mediated by Apg16 oligomerization, is essential for autophagy in yeast. The Journal of biological chemistry 277: 18619–18625.
Kuroyanagi H, Yan J, Seki N, Yamanouchi Y, Suzuki Y, Takano T, Muramatsu M, Shirasawa T. 1998. Human ULK1, a Novel Serine/Threonine Kinase Related to UNC-51 Kinase of Caenorhabditis elegans: cDNA Cloning, Expression, and Chromosomal Assignment. Genomics 51: 76–85.
Lu Q, Yang P, Huang X, Hu W, Guo B, Wu F, Lin L, Kovacs AL, Yu L, Zhang H. 2011. The WD40 repeat PtdIns(3)P-binding protein EPG-6 regulates progression of omegasomes to autophagosomes. Dev Cell 21: 343–357.
Matsuura A, Miki T, Wada Y, Ohsumi Y. 1997. Apg1p, a novel protein kinase required for the autophagic process in Saccharomyces cerevisiae. Gene 192: 245–250.
Meléndez A, Talloczy Z, Seaman M, Eskelinen EL, Hall DH, Levine B. 2003. Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301: 1387–1391.
Mizushima N, Kuma A, Kobayashi Y, Yamamoto A, Matsubae M, Takao T, Natsume T, Ohsumi Y, Yoshimori T. 2003. Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate. Journal of Cell Science 116: 1679–1688.
Mizushima N, Sugita H, Yoshimori T, Ohsumi Y. 1998. A New Protein Conjugation System in Human THE COUNTERPART OF THE YEAST Apg12p CONJUGATION SYSTEM ESSENTIAL FOR AUTOPHAGY*. The Journal of biological chemistry 273: 33889–33892.
Mizushima N, Yamamoto A, Hatano M, Kobayashi Y, Kabeya Y, Suzuki K, Tokuhisa T, Ohsumi Y, Yoshimori T. 2001. Dissection of Autophagosome Formation using Apg5-deficient Mouse Embryonic Stem Cells. Journal of Cell Biology 152: 657–667.
Mizushima N, Yoshimori T, Ohsumi Y. 2002. Mouse Apg10 as an Apg12-conjugating enzyme: analysis by the conjugation-mediated yeast two-hybrid Method. FEBS letters 532: 450–454.
Noda T, Kim J, Huang WP, Baba M, Tokunaga C, Ohsumi Y, Klionsky DJ. 2000. Apg9p/Cvt7p is an integral membrane protein required for transport vesicle formation in the Cvt and autophagy pathways. The Journal of cell biology 148: 465–480.
Noda T, Ohsumi Y. 1998. Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. The Journal of biological chemistry 273: 3963–3966.
Obara K, Sekito T, Ohsumi Y. 2006. Assortment of phosphatidylinositol 3-kinase complexes--Atg14p directs association of complex I to the pre-autophagosomal structure in Saccharomyces cerevisiae. Molecular biology of the cell 17: 1527–1539.
Ogura K, Wicky C, Magnenat L, Tobler H, Mori I, Muller F, Ohshima Y. 1994. Caenorhabditis elegans unc-51 gene required for axonal elongation encodes a novel serine/threonine kinase. Genes & development 8: 2389–2400.
Panaretou C, Domin J, Cockcroft S, Waterfield MD. 1997. Characterization of p150, an Adaptor Protein for the Human Phosphatidylinositol (PtdIns) 3-Kinase. Journal of Biological Chemistry 272: 2477–2485.
Polson HE, de Lartigue J, Rigden D, Reedijk M, Urbé S, Clague M, Tooze S. 2010. Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phagophores and positively regulates LC3 lipidation. Autophagy 6: 506–522.
Reggiori F, and Klionsky, D. J. 2006. Atg9 sorting from mitochondria is impaired in early secretion and VFT-complex mutants in Saccharomyces cerevisiae. Journal of Cell Science 119: 2903–2911.
Roggo L, Bernard V, Kovacs AL, Rose AM, Savoy F, Zetka M, Wymann MP, Muller F. 2002. Membrane transport in Caenorhabditis elegans: an essential role for VPS34 at the nuclear membrane. The EMBO journal 21: 1673–1683.
Ruck A, Attonito J, Garces KT, Nunez L, Palmisano NJ, Rubel Z, Bai Z, Nguyen KC, Sun L, Grant BD et al. 2011. The Atg6/Vps30/Beclin1 ortholog BEC-1 mediates endocytic retrograde transport in addition to autophagy in C. elegans. Autophagy 7.
Seaman MNJ, Marcusson EG, Cereghino JL, Emr SD. 1997. Endosome to Golgi Retrieval of the Vacuolar Protein Sorting Receptor, Vps10p, Requires the Function of the VPS29, VPS30, and VPS35Gene Products. Journal of Cell Biology 137: 79–92.
Seglen PO, Gordon PB. 1982. 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proceedings of the National Academy of Sciences of the United States of America 79: 1889–1892.
Shintani T, Suzuki, K., Kamada, Y., Noda, T., and Ohsumi, Y. 2001. Apg2p functions in autophagosome formation on the perivacuolar structure. Journal of Biological Chemistry 276: 30452–30460.
Sun Q, Fan W, Chen K, Ding X, Chen S, Zhong Q. 2008. Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase. Proceedings of the National Academy of Sciences of the United States of America 105: 19211–19216.
Takacs-Vellai K, Vellai T, Puoti A, Passannante M, Wicky C, Streit A, Kovacs AL, Muller F. 2005. Inactivation of the autophagy gene bec-1 triggers apoptotic cell death in C. elegans. Current biology : CB 15: 1513–1517.
Takahiro Shintani NM, Yoko Ogawa, Akira Matsuura, Takeshi Noda and Yoshinori Ohsumi. 1999. Apg10p, a novel protein-conjugating enzyme essential for autophagy in yeast. The EMBO journal 18: 5234–5241.
Tanida I, Sou YS, Ezaki J, Minematsu-Ikeguchi N, Ueno T, Kominami E. 2004. HsAtg4B/HsApg4B/autophagin-1 cleaves the carboxyl termini of three human Atg8 homologues and delipidates microtubule-associated protein light chain 3- and GABAA receptor-associated protein-phospholipid conjugates. The Journal of biological chemistry 279: 36268–36276.
Tanida I, Tanida-Miyake E, Komatsu M, Ueno T, Kominami E. 2002. Human Apg3p/Aut1p homologue is an authentic E2 enzyme for multiple substrates, GATE-16, GABARAP, and MAP-LC3, and facilitates the conjugation of hApg12p to hApg5p. The Journal of biological chemistry 277: 13739–13744.
Tanida I, Tanida-Miyake E, Ueno T, Kominami E. 2001. The human homolog of Saccharomyces cerevisiae Apg7p is a Protein-activating enzyme for multiple substrates including human Apg12p, GATE-16, GABARAP, and MAP-LC3. The Journal of biological chemistry 276: 1701–1706.
Tian E, Wang F, Han Ja, Zhang H. 2009. epg-1 functions in autophagy-regulated processes and may encode a highly divergent Atg13 homolog in C. elegans. Autophagy 5: 608–615.
Tian Y, Li Z, Hu W, Ren H, Tian E, Zhao Y, Lu Q, Huang X, Yang P, Li X et al. 2010. C. elegans screen identifies autophagy genes specific to multicellular organisms. Cell 141: 1042–1055.
Vellai T, Takacs-Vellai K, Zhang Y, Kovacs AL, Orosz L, Muller F. 2003. Genetics: influence of TOR kinase on lifespan in C. elegans. Nature 426: 620.
Volinia S, Dhand R, Vanhaesebroeck B, MacDougall LK, Stein R, Zvelebil MJ, Domin J, Panaretou C, Waterfield MD. 1995. A human phosphatidylinositol 3-kinase complex related to the yeast Vps34p-Vps15p protein sorting system. The EMBO journal 14: 3339–3348.
Wang CW, Kim J, Huang WP, Abeliovich H, Stromhaug PE, Dunn WA, Jr., Klionsky DJ. 2001. Apg2 is a novel protein required for the cytoplasm to vacuole targeting, autophagy, and pexophagy pathways. The Journal of biological chemistry 276: 30442–30451.
Yamada T, Carson AR, Caniggia I, Umebayashi K, Yoshimori T, Nakabayashi K, Scherer SW. 2005. Endothelial nitric-oxide synthase antisense (NOS3AS) gene encodes an autophagy-related protein (APG9-like2) highly expressed in trophoblast. The Journal of biological chemistry 280: 18283–18290.
Yang P, Zhang H. 2011. The coiled-coil domain protein EPG-8 plays an essential role in the autophagy pathway in C. elegans. Autophagy 7: 159–165.
Zhang Y, Yan L, Zhou Z, Yang P, Tian E, Zhang K, Zhao Y, Li Z, Song B, Han J et al. 2009. SEPA-1 mediates the specific recognition and degradation of P granule components by autophagy in C. elegans. Cell 136: 308–321.
Zhao Y, Tian E, Zhang H. 2009. Selective autophagic degradation of maternally-loaded germline P granule components in somatic cells during C. elegans embryogenesis. Autophagy 5: 717–719.