Dynamic regulation of macroautophagy by distinctive ubiquitin-like proteins (original) (raw)

• Yang, Z. & Klionsky, D.J. Eaten alive: a history of macroautophagy. Nat. Cell Biol. 12, 814–822 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Reggiori, F. & Klionsky, D.J. Autophagic processes in yeast: mechanism, machinery and regulation. Genetics 194, 341–361 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Mijaljica, D. et al. Receptor protein complexes are in control of autophagy. Autophagy 8, 1701–1705 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Oku, M. & Sakai, Y. Peroxisomes as dynamic organelles: autophagic degradation. FEBS J. 277, 3289–3294 (2010).
  Article CAS PubMed Google Scholar
• Kanki, T., Klionsky, D.J. & Okamoto, K. Mitochondria autophagy in yeast. Antioxid. Redox Signal. 14, 1989–2001 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Youle, R.J. & Narendra, D.P. Mechanisms of mitophagy. Nat. Rev. Mol. Cell Biol. 12, 9–14 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Knodler, L.A. & Celli, J. Eating the strangers within: host control of intracellular bacteria via xenophagy. Cell. Microbiol. 13, 1319–1327 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Geng, J. & Klionsky, D.J. The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy. EMBO Rep. 9, 859–864 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Ichimura, Y. et al. A ubiquitin-like system mediates protein lipidation. Nature 408, 488–492 (2000).Identifies the Atg8–PE conjugation system.
  Article CAS PubMed Google Scholar
• Mizushima, N. et al. A protein conjugation system essential for autophagy. Nature 395, 395–398 (1998).Identifies the Atg12–Atg5 conjugation system.
  Article CAS PubMed Google Scholar
• Weidberg, H. et al. LC3 and GATE-16/GABARAP subfamilies are both essential yet act differently in autophagosome biogenesis. EMBO J. 29, 1792–1802 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Xie, Z., Nair, U. & Klionsky, D.J. Atg8 controls phagophore expansion during autophagosome formation. Mol. Biol. Cell 19, 3290–3298 (2008).Shows that Atg8 levels correlate with the size of autophagosomes.
  Article CAS PubMed PubMed Central Google Scholar
• Nakatogawa, H., Ichimura, Y. & Ohsumi, Y. Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion. Cell 130, 165–178 (2007).
  Article CAS PubMed Google Scholar
• Nair, U. et al. SNARE proteins are required for macroautophagy. Cell 146, 290–302 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Nair, U. et al. A role for Atg8-PE deconjugation in autophagosome biogenesis. Autophagy 8, 780–793 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Shintani, T., Huang, W.-P., Stromhaug, P.E. & Klionsky, D.J. Mechanism of cargo selection in the cytoplasm to vacuole targeting pathway. Dev. Cell 3, 825–837 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Hanada, T. et al. The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy. J Biol. Chem. 282, 37298–37302 (2007).Identifies the Atg12–Atg5 complex as a new E3 ligase promoting Atg8 lipidation.
  Article CAS PubMed Google Scholar
• Kuma, A., Mizushima, N., Ishihara, N. & Ohsumi, Y. Formation of the approximately 350-kDa Apg12-Apg5•Apg16 multimeric complex, mediated by Apg16 oligomerization, is essential for autophagy in yeast. J. Biol. Chem. 277, 18619–18625 (2002).
  Article CAS PubMed Google Scholar
• Fujita, N. et al. The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy. Mol. Biol. Cell 19, 2092–2100 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Kraft, C. et al. Binding of the Atg1/ULK1 kinase to the ubiquitin-like protein Atg8 regulates autophagy. EMBO J. 31, 3691–3703 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Noda, N.N., Ohsumi, Y. & Inagaki, F. Atg8-family interacting motif crucial for selective autophagy. FEBS Lett. 584, 1379–1385 (2010).
  Article CAS PubMed Google Scholar
• Noda, N.N. et al. Structural basis of target recognition by Atg8/LC3 during selective autophagy. Genes Cells 13, 1211–1218 (2008).Refs. 22 and 44 identify the structural basis for AIM or LIR binding to Atg8 (LC3) UBLs.
  Article CAS PubMed Google Scholar
• Behrends, C., Sowa, M.E., Gygi, S.P. & Harper, J.W. Network organization of the human autophagy system. Nature 466, 68–76 (2010).A proteomic analysis of Atg8 (LC3) family–interacting proteins, suggesting the complexity of the autophagy network.
  Article CAS PubMed PubMed Central Google Scholar
• Noda, N.N. et al. Structural basis of Atg8 activation by a homodimeric E1, Atg7. Mol. Cell 44, 462–475 (2011).Refs. 24, 69 and 70 revealed mechanisms by which Atg7 initiates conjugation of autophagy UBLs.
  Article CAS PubMed Google Scholar
• Satoo, K. et al. The structure of Atg4B–LC3 complex reveals the mechanism of LC3 processing and delipidation during autophagy. EMBO J. 28, 1341–1350 (2009).Revealed the structural mechanisms underlying ATG4-dependent processing and deconjugation of LC3 family members.
  Article CAS PubMed PubMed Central Google Scholar
• Suzuki, H. et al. Structural basis of the autophagy-related LC3/Atg13 LIR complex: recognition and interaction mechanism. Structure 22, 47–58 (2014).
  Article CAS PubMed Google Scholar
• Pankiv, S. et al. FYCO1 is a Rab7 effector that binds to LC3 and PI3P to mediate microtubule plus end-directed vesicle transport. J. Cell Biol. 188, 253–269 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Seillier, M. et al. TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell death. Cell Death Differ. 19, 1525–1535 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Colecchia, D. et al. MAPK15/ERK8 stimulates autophagy by interacting with LC3 and GABARAP proteins. Autophagy 8, 1724–1740 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Popovic, D. et al. Rab GTPase-activating proteins in autophagy: regulation of endocytic and autophagy pathways by direct binding to human ATG8 modifiers. Mol. Cell. Biol. 32, 1733–1744 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Nowak, J. et al. The TP53INP2 protein is required for autophagy in mammalian cells. Mol. Biol. Cell 20, 870–881 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Birgisdottir, Å.B., Lamark, T. & Johansen, T. The LIR motif: crucial for selective autophagy. J. Cell Sci. 126, 3237–3247 (2013).
  Article CAS PubMed Google Scholar
• Lynch-Day, M.A. & Klionsky, D.J. The Cvt pathway as a model for selective autophagy. FEBS Lett. 584, 1359–1366 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Kanki, T., Wang, K., Cao, Y., Baba, M. & Klionsky, D.J. Atg32 is a mitochondrial protein that confers selectivity during mitophagy. Dev. Cell 17, 98–109 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Okamoto, K., Kondo-Okamoto, N. & Ohsumi, Y. Mitochondria-anchored receptor Atg32 mediates degradation of mitochondria via selective autophagy. Dev. Cell 17, 87–97 (2009).
  Article CAS PubMed Google Scholar
• Motley, A.M., Nuttall, J.M. & Hettema, E.H. Pex3-anchored Atg36 tags peroxisomes for degradation in Saccharomyces cerevisiae. EMBO J. 31, 2852–2868 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Shaid, S., Brandts, C.H., Serve, H. & Dikic, I. Ubiquitination and selective autophagy. Cell Death Differ. 20, 21–30 (2013).
  Article CAS PubMed Google Scholar
• Pankiv, S. et al. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J. Biol. Chem. 282, 24131–24145 (2007).
  Article CAS PubMed Google Scholar
• Kirkin, V. et al. A role for NBR1 in autophagosomal degradation of ubiquitinated substrates. Mol. Cell 33, 505–516 (2009).
  Article CAS PubMed Google Scholar
• Thurston, T.L., Ryzhakov, G., Bloor, S., von Muhlinen, N. & Randow, F. The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria. Nat. Immunol. 10, 1215–1221 (2009).
  Article CAS PubMed Google Scholar
• Johansen, T. & Lamark, T. Selective autophagy mediated by autophagic adapter proteins. Autophagy 7, 279–296 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Korac, J. et al. Ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates. J. Cell Sci. 126, 580–592 (2013).
  Article CAS PubMed Google Scholar
• Jiang, S., Wells, C.D. & Roach, P.J. Starch-binding domain-containing protein 1 (Stbd1) and glycogen metabolism: identification of the Atg8 family interacting motif (AIM) in Stbd1 required for interaction with GABARAPL1. Biochem. Biophys. Res. Commun. 413, 420–425 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Ichimura, Y. et al. Structural basis for sorting mechanism of p62 in selective autophagy. J. Biol. Chem. 283, 22847–22857 (2008).
  Article CAS PubMed Google Scholar
• Rozenknop, A. et al. Characterization of the interaction of GABARAPL-1 with the LIR motif of NBR1. J. Mol. Biol. 410, 477–487 (2011).
  Article CAS PubMed Google Scholar
• Kaufmann, A., Beier, V., Franquelim, H.G. & Wollert, T. Molecular mechanism of autophagic membrane-scaffold assembly and disassembly. Cell 156, 469–481 (2014).
  Article CAS PubMed Google Scholar
• Birmingham, C.L., Smith, A.C., Bakowski, M.A., Yoshimori, T. & Brumell, J.H. Autophagy controls Salmonella infection in response to damage to the _Salmonella_-containing vacuole. J. Biol. Chem. 281, 11374–11383 (2006).
  Article CAS PubMed Google Scholar
• Thurston, T.L., Wandel, M.P., von Muhlinen, N., Foeglein, A. & Randow, F. Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion. Nature 482, 414–418 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• von Muhlinen, N. et al. LC3C, bound selectively by a noncanonical LIR motif in NDP52, is required for antibacterial autophagy. Mol. Cell 48, 329–342 (2012).Revealed basis for LC3C specificity toward a CLIR.
  Article CAS PubMed PubMed Central Google Scholar
• Wild, P. et al. Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science 333, 228–233 (2011).Refs. 50 and 51 demonstrated phosphorylation-dependent recruitment of cargo to Atg8 (LC3) family members.
  Article CAS PubMed PubMed Central Google Scholar
• Rogov, V.V. et al. Structural basis for phosphorylation-triggered autophagic clearance of Salmonella. Biochem. J. 454, 459–466 (2013).
  Article CAS PubMed Google Scholar
• Weiergräber, O.H. et al. Ligand binding mode of GABAA receptor-associated protein. J. Mol. Biol. 381, 1320–1331 (2008).
  Article PubMed CAS Google Scholar
• Komander, D. & Rape, M. The ubiquitin code. Annu. Rev. Biochem. 81, 203–229 (2012).
  Article CAS PubMed Google Scholar
• Kirisako, T. et al. The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway. J. Cell Biol. 151, 263–276 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Li, M. et al. Kinetics comparisons of mammalian Atg4 homologues indicate selective preferences toward diverse Atg8 substrates. J. Biol. Chem. 286, 7327–7338 (2011).
  Article CAS PubMed Google Scholar
• Kabeya, Y. et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 19, 5720–5728 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Hemelaar, J., Lelyveld, V.S., Kessler, B.M. & Ploegh, H.L. A single protease, Apg4B, is specific for the autophagy-related ubiquitin-like proteins GATE-16, MAP1–LC3, GABARAP, and Apg8L. J. Biol. Chem. 278, 51841–51850 (2003).
  Article CAS PubMed Google Scholar
• Kabeya, Y. et al. LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J. Cell Sci. 117, 2805–2812 (2004).
  Article CAS PubMed Google Scholar
• Mariño, G. et al. Human autophagins, a family of cysteine proteinases potentially implicated in cell degradation by autophagy. J. Biol. Chem. 278, 3671–3678 (2003).
  Article PubMed CAS Google Scholar
• Tanida, I., Ueno, T. & Kominami, E. Human light chain 3/MAP1LC3B is cleaved at its carboxyl-terminal Met121 to expose Gly120 for lipidation and targeting to autophagosomal membranes. J. Biol. Chem. 279, 47704–47710 (2004).
  Article CAS PubMed Google Scholar
• Yu, Z.Q. et al. Dual roles of Atg8-PE deconjugation by Atg4 in autophagy. Autophagy 8, 883–892 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Kumanomidou, T. et al. The crystal structure of human Atg4b, a processing and de-conjugating enzyme for autophagosome-forming modifiers. J. Mol. Biol. 355, 612–618 (2006).
  Article CAS PubMed Google Scholar
• Sugawara, K. et al. Structural basis for the specificity and catalysis of human Atg4B responsible for mammalian autophagy. J. Biol. Chem. 280, 40058–40065 (2005).
  Article CAS PubMed Google Scholar
• Sakoh-Nakatogawa, M. et al. Atg12–Atg5 conjugate enhances E2 activity of Atg3 by rearranging its catalytic site. Nat. Struct. Mol. Biol. 20, 433–439 (2013).
  Article CAS PubMed Google Scholar
• Noda, N.N., Fujioka, Y., Hanada, T., Ohsumi, Y. & Inagaki, F. Structure of the Atg12–Atg5 conjugate reveals a platform for stimulating Atg8–PE conjugation. EMBO Rep. 14, 206–211 (2013).Refs. 65 and 79 revealed the structure of the Atg12–Atg5 conjugate.
  Article CAS PubMed Google Scholar
• Radoshevich, L. et al. ATG12 conjugation to ATG3 regulates mitochondrial homeostasis and cell death. Cell 142, 590–600 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Tanida, I. et al. Apg7p/Cvt2p: a novel protein-activating enzyme essential for autophagy. Mol. Biol. Cell 10, 1367–1379 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Schulman, B.A. & Harper, J.W. Ubiquitin-like protein activation by E1 enzymes: the apex for downstream signalling pathways. Nat. Rev. Mol. Cell Biol. 10, 319–331 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Taherbhoy, A.M. et al. Atg8 transfer from Atg7 to Atg3: a distinctive E1–E2 architecture and mechanism in the autophagy pathway. Mol. Cell 44, 451–461 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Hong, S.B. et al. Insights into noncanonical E1 enzyme activation from the structure of autophagic E1 Atg7 with Atg8. Nat. Struct. Mol. Biol. 18, 1323–1330 (2011).
  Article CAS PubMed Google Scholar
• Kaiser, S.E. et al. Noncanonical E2 recruitment by the autophagy E1 revealed by Atg7–Atg3 and Atg7–Atg10 structures. Nat. Struct. Mol. Biol. 19, 1242–1249 (2012).Refs. 71 and 72 revealed mechanisms of Atg7 interactions with the autophagy E2s Atg3 and Atg10.
  Article CAS PubMed PubMed Central Google Scholar
• Yamaguchi, M. et al. Noncanonical recognition and UBL loading of distinct E2s by autophagy-essential Atg7. Nat. Struct. Mol. Biol. 19, 1250–1256 (2012).
  Article CAS PubMed Google Scholar
• Komatsu, M. et al. The C-terminal region of an Apg7p/Cvt2p is required for homodimerization and is essential for its E1 activity and E1–E2 complex formation. J. Biol. Chem. 276, 9846–9854 (2001).
  Article CAS PubMed Google Scholar
• Hong, S.B., Kim, B.W., Kim, J.H. & Song, H.K. Structure of the autophagic E2 enzyme Atg10. Acta Crystallogr. D Biol. Crystallogr. 68, 1409–1417 (2012).
  Article CAS PubMed Google Scholar
• Yamada, Y. et al. The crystal structure of Atg3, an autophagy-related ubiquitin carrier protein (E2) enzyme that mediates Atg8 lipidation. J. Biol. Chem. 282, 8036–8043 (2007).
  Article CAS PubMed Google Scholar
• Yamaguchi, M. et al. Structural insights into Atg10-mediated formation of the autophagy-essential Atg12-Atg5 conjugate. Structure 20, 1244–1254 (2012).
  Article CAS PubMed Google Scholar
• Cao, Y., Cheong, H., Song, H. & Klionsky, D.J. In vivo reconstitution of autophagy in Saccharomyces cerevisiae. J. Cell Biol. 182, 703–713 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Romanov, J. et al. Mechanism and functions of membrane binding by the Atg5–Atg12/Atg16 complex during autophagosome formation. EMBO J. 31, 4304–4317 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Otomo, C., Metlagel, Z., Takaesu, G. & Otomo, T. Structure of the human ATG12∼ATG5 conjugate required for LC3 lipidation in autophagy. Nat. Struct. Mol. Biol. 20, 59–66 (2012).
  Article PubMed PubMed Central CAS Google Scholar
• Metlagel, Z., Otomo, C., Takaesu, G. & Otomo, T. Structural basis of ATG3 recognition by the autophagic ubiquitin-like protein ATG12. Proc. Natl. Acad. Sci. USA 110, 18844–18849 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Brownell, J.E. et al. Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ. Mol. Cell 37, 102–111 (2010).
  Article CAS PubMed Google Scholar
• Boada-Romero, E. et al. TMEM59 defines a novel ATG16L1-binding motif that promotes local activation of LC3. EMBO J. 32, 566–582 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Travassos, L.H. et al. Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat. Immunol. 11, 55–62 (2010).
  Article CAS PubMed Google Scholar
• Nakagawa, I. et al. Autophagy defends cells against invading group A Streptococcus. Science 306, 1037–1040 (2004).
  Article CAS PubMed Google Scholar
• Hwang, S. et al. Nondegradative role of Atg5-Atg12/ Atg16L1 autophagy protein complex in antiviral activity of interferon gamma. Cell Host Microbe 11, 397–409 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Cadwell, K., Patel, K.K., Komatsu, M., Virgin, H.W. IV & Stappenbeck, T.S. A common role for Atg16L1, Atg5 and Atg7 in small intestinal Paneth cells and Crohn disease. Autophagy 5, 250–252 (2009).
  Article CAS PubMed Google Scholar
• Tanji, K., Mori, F., Kakita, A., Takahashi, H. & Wakabayashi, K. Alteration of autophagosomal proteins (LC3, GABARAP and GATE-16) in Lewy body disease. Neurobiol. Dis. 43, 690–697 (2011).
  Article CAS PubMed Google Scholar
• Chen, D. et al. Genetic analysis of the ATG7 gene promoter in sporadic Parkinson’s disease. Neurosci. Lett. 534, 193–198 (2013).
  Article CAS PubMed Google Scholar
• Chen, D. et al. A novel and functional variant within the ATG5 gene promoter in sporadic Parkinson’s disease. Neurosci. Lett. 538, 49–53 (2013).
  Article CAS PubMed Google Scholar
• Metzger, S. et al. Age at onset in Huntington’s disease is modified by the autophagy pathway: implication of the V471A polymorphism in Atg7. Hum. Genet. 128, 453–459 (2010).
  Article CAS PubMed Google Scholar
• Komatsu, M. et al. Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J. Cell Biol. 169, 425–434 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Ding, W.X. et al. Autophagy reduces acute ethanol-induced hepatotoxicity and steatosis in mice. Gastroenterology 139, 1740–1752 (2010).
  Article CAS PubMed Google Scholar
• Takamura, A. et al. Autophagy-deficient mice develop multiple liver tumors. Genes Dev. 25, 795–800 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Hara, T. et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441, 885–889 (2006).Refs. 94 and 95 show that neuron-specific loss of ATG5 or ATG7 leads to neurodegeneration.
  Article CAS PubMed Google Scholar
• Komatsu, M. et al. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441, 880–884 (2006).
  Article CAS PubMed Google Scholar
• Masiero, E. et al. Autophagy is required to maintain muscle mass. Cell Metab. 10, 507–515 (2009).
  Article CAS PubMed Google Scholar
• Raben, N. et al. Suppression of autophagy in skeletal muscle uncovers the accumulation of ubiquitinated proteins and their potential role in muscle damage in Pompe disease. Hum. Mol. Genet. 17, 3897–3908 (2008).
  CAS PubMed PubMed Central Google Scholar
• Saitoh, T. et al. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1β production. Nature 456, 264–268 (2008).
  Article CAS PubMed Google Scholar
• Cadwell, K. et al. A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 456, 259–263 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Hampe, J. et al. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat. Genet. 39, 207–211 (2007).
  Article CAS PubMed Google Scholar
• Rioux, J.D. et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat. Genet. 39, 596–604 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Novak, I. et al. Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep. 11, 45–51 (2010).Refs. 102 and 103 show that BNIP3L (Nix) is a mitophagy receptor that binds LC3.
  Article CAS PubMed Google Scholar
• Sandoval, H. et al. Essential role for Nix in autophagic maturation of erythroid cells. Nature 454, 232–235 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Kuma, A. et al. The role of autophagy during the early neonatal starvation period. Nature 432, 1032–1036 (2004).
  Article CAS PubMed Google Scholar
• Tsukamoto, S. et al. Autophagy is essential for preimplantation development of mouse embryos. Science 321, 117–120 (2008).
  Article CAS PubMed Google Scholar
• Mortensen, M. et al. The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance. J. Exp. Med. 208, 455–467 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Kitamura, K. et al. Autophagy-related Atg8 localizes to the apicoplast of the human malaria parasite Plasmodium falciparum. PLoS ONE 7, e42977 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Scherz-Shouval, R. et al. Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J. 26, 1749–1760 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Nair, U., Cao, Y., Xie, Z. & Klionsky, D.J. Roles of the lipid-binding motifs of Atg18 and Atg21 in the cytoplasm to vacuole targeting pathway and autophagy. J. Biol. Chem. 285, 11476–11488 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Thompson, A.R., Doelling, J.H., Suttangkakul, A. & Vierstra, R.D. Autophagic nutrient recycling in Arabidopsis directed by the ATG8 and ATG12 conjugation pathways. Plant Physiol. 138, 2097–2110 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Mizushima, N. et al. Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells. J. Cell Biol. 152, 657–668 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Hain, A.U.P. et al. Structural characterization and inhibition of the Plasmodium Atg8-Atg3 interaction. J. Struct. Biol. 180, 551–562 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Yamaguchi, M. et al. Autophagy-related protein 8 (Atg8) family interacting motif in Atg3 mediates the Atg3-Atg8 interaction and is crucial for the cytoplasm-to-vacuole targeting pathway. J. Biol. Chem. 285, 29599–29607 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Martinez, J. et al. Microtubule-associated protein 1 light chain 3 alpha (LC3)-associated phagocytosis is required for the efficient clearance of dead cells. Proc. Natl. Acad. Sci. USA 108, 17396–17401 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Ishibashi, K., Uemura, T., Waguri, S. & Fukuda, M. Atg16L1, an essential factor for canonical autophagy, participates in hormone secretion from PC12 cells independently of autophagic activity. Mol. Biol. Cell 23, 3193–3202 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Yousefi, S. et al. Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat. Cell Biol. 8, 1124–1132 (2006).
  Article CAS PubMed Google Scholar
• Lee, I. & Schindelin, H. Structural insights into E1-catalyzed ubiquitin activation and transfer to conjugating enzymes. Cell 134, 268–278 (2008).
  Article CAS PubMed Google Scholar