During autophagy, cytosol, protein aggregates, and organelles are sequestered into double-membrane vesicles called autophagosomes and delivered to the lysosome/vacuole for breakdown and recycling of their basic components. In all eukaryotes this pathway is important for adaptation to stress conditions such as nutrient deprivation, as well as to regulate intracellular homeostasis by adjusting organelle number and clearing damaged structures. For a long time, starvation-induced autophagy has been viewed as a nonselective transport pathway; however, recent studies have revealed that autophagy is able to selectively engulf specific structures, ranging from proteins to entire organelles. In this paper, we discuss recent findings on the mechanisms and physiological implications of two selective types of autophagy: ribophagy, the specific degradation of ribosomes, and reticulophagy, the selective elimination of portions of the ER. 1. Introduction Autophagy is a degradative process that allows cells to maintain their homeostasis in numerous physiological situations. It is required, for example, to face prolonged starvation periods and nutritional fluctuations in the environment, developmental tissue remodeling, organelle quality control, and immune responses [1, 2]. In addition, this pathway has been implicated in the physiopathology of multiple diseases [3, 4]. Autophagosomes are the hallmark of autophagy. These double-membrane vesicles are generated in the cytosol and during their formation they engulf the cargo to be delivered into the mammalian lysosomes or yeast and plant vacuoles for degradation [5]. Two types of autophagy have been described: selective and non-selective autophagy. During non-selective autophagy bulk cytosol, including organelles, is randomly sequestered into autophagosomes. On the other hand, during selective autophagy, a specific cargo is exclusively enwrapped by double-membrane vesicles, which contain little cytoplasm with their size corresponding to that of their cargo [6]. Autophagy progression relies on the function of the autophagy-related (Atg) proteins that mediate autophagosome biogenesis, selective cargo recognition, fusion with the lysosome/vacuole, or vesicle breakdown [5, 7, 8]. Upon nutritional stresses, fractions of the cytoplasm are consumed via autophagy and the resulting catabolic products are used as sources of energy or as building blocks for the synthesis of new macromolecules. In these situations autophagy is mainly considered as a non-selective process. Nonetheless an increasing number of selective types of
References
[1]
B. Levine, N. Mizushima, and H. W. Virgin, “Autophagy in immunity and inflammation,” Nature, vol. 469, no. 7330, pp. 323–335, 2011.
[2]
N. Mizushima and B. Levine, “Autophagy in mammalian development and differentiation,” Nature Cell Biology, vol. 12, no. 9, pp. 823–830, 2010.
[3]
B. Levine and G. Kroemer, “Autophagy in the pathogenesis of disease,” Cell, vol. 132, no. 1, pp. 27–42, 2008.
[4]
N. Mizushima, B. Levine, A. M. Cuervo, and D. J. Klionsky, “Autophagy fights disease through cellular self-digestion,” Nature, vol. 451, no. 7182, pp. 1069–1075, 2008.
[5]
H. Nakatogawa, K. Suzuki, Y. Kamada, and Y. Ohsumi, “Dynamics and diversity in autophagy mechanisms: lessons from yeast,” Nature Reviews Molecular Cell Biology, vol. 10, no. 7, pp. 458–467, 2009.
[6]
C. Kraft, F. Reggiori, and M. Peter, “Selective types of autophagy in yeast,” Biochimica et Biophysica Acta, vol. 1793, no. 9, pp. 1404–1412, 2009.
[7]
Z. Yang and D. J. Klionsky, “Mammalian autophagy: core molecular machinery and signaling regulation,” Current Opinion in Cell Biology, vol. 22, no. 2, pp. 124–131, 2010.
[8]
T. Yoshimori and T. Noda, “Toward unraveling membrane biogenesis in mammalian autophagy,” Current Opinion in Cell Biology, vol. 20, no. 4, pp. 401–407, 2008.
[9]
M. Komatsu and Y. Ichimura, “Selective autophagy regulates various cellular functions,” Genes to Cells, vol. 15, no. 9, pp. 923–933, 2010.
[10]
M. U. Hutchins and D. J. Klionsky, “Vacuolar localization of oligomeric α-mannosidase requires the cytoplasm to vacuole targeting and autophagy pathway components in Saccharomyces cerevisiae,” Journal of Biological Chemistry, vol. 276, no. 23, pp. 20491–20498, 2001.
[11]
S. V. Scott, M. Baba, Y. Ohsumi, and D. J. Klionsky, “Aminopeptidase I is targeted to the vacuole by a nonclassical vesicular mechanism,” Journal of Cell Biology, vol. 138, no. 1, pp. 37–44, 1997.
[12]
M. A. Lynch-Day and D. J. Klionsky, “The Cvt pathway as a model for selective autophagy,” FEBS Letters, vol. 584, no. 7, pp. 1359–1366, 2010.
[13]
M. Yuga, K. Gomi, D. J. Klionsky, and T. Shintani, “Aspartyl aminopeptidase is imported from the cytoplasm to the vacuole by selective autophagy in Saccharomyces cerevisiae,” Journal of Biological Chemistry, vol. 286, no. 15, pp. 13704–13713, 2011.
[14]
T. Shintani and D. J. Klionsky, “Cargo proteins facilitate the formation of transport vesicles in the cytoplasm to vacuole targeting pathway,” Journal of Biological Chemistry, vol. 279, no. 29, pp. 29889–29894, 2004.
[15]
R. Manjithaya, T. Y. Nazarko, J. C. Farré, and S. S. Suresh, “Molecular mechanism and physiological role of pexophagy,” FEBS Letters, vol. 584, no. 7, pp. 1367–1373, 2010.
[16]
K. Wang and D. J. Klionsky, “Mitochondria removal by autophagy,” Autophagy, vol. 7, no. 3, pp. 297–300, 2011.
[17]
C. Kraft, M. Peter, and K. Hofmann, “Selective autophagy: ubiquitin-mediated recognition and beyond,” Nature Cell Biology, vol. 12, no. 9, pp. 836–841, 2010.
[18]
T. P. Ashford and K. R. Porter, “Cytoplasmic components in hepatic cell lysosomes,” Journal of Cell Biology, vol. 12, pp. 198–202, 1962.
[19]
E. L. Eskelinen, F. Reggiori, M. Baba, A. L. Kovács, and P. O. Seglen, “Seeing is believing: the impact of electron microscopy on autophagy research,” Autophagy, vol. 7, no. 9, pp. 935–956, 2011.
[20]
C. Kraft, A. Deplazes, M. Sohrmann, and M. Peter, “Mature ribosomes are selectively degraded upon starvation by an autophagy pathway requiring the Ubp3p/Bre5p ubiquitin protease,” Nature Cell Biology, vol. 10, no. 5, pp. 602–610, 2008.
[21]
B. K. Baxter, H. Abeliovich, X. Zhang, A. G. Stirling, A. L. Burlingame, and D. S. Goldfarb, “Atg19p ubiquitination and the cytoplasm to vacuole trafficking pathway in yeast,” Journal of Biological Chemistry, vol. 280, no. 47, pp. 39067–39076, 2005.
[22]
S. V. Scott, J. Guan, M. U. Hutchins, J. Kim, and D. J. Klionsky, “Cvt19 is a receptor for the cytoplasm-to-vacuole targeting pathway,” Molecular Cell, vol. 7, no. 6, pp. 1131–1141, 2001.
[23]
C. Kraft and M. Peter, “Is the Rsp5 ubiquitin ligase involved in the regulation of ribophagy?” Autophagy, vol. 4, no. 6, pp. 838–840, 2008.
[24]
C. Pohl and S. Jentsch, “Midbody ring disposal by autophagy is a post-abscission event of cytokinesis,” Nature Cell Biology, vol. 11, no. 1, pp. 65–70, 2009.
[25]
J. R. Warner, “The economics of ribosome biosynthesis in yeast,” Trends in Biochemical Sciences, vol. 24, no. 11, pp. 437–440, 1999.
[26]
M. S. Hillwig, A. L. Contento, A. Meyer, D. Ebany, D. C. Bassham, and G. C. MacIntosha, “RNS2, a conserved member of the RNase T2 family, is necessary for ribosomal RNA decay in plants,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 3, pp. 1093–1098, 2011.
[27]
A. R. Kristensen, S. Schandorff, M. H？yer-Hansen et al., “Ordered organelle degradation during starvation-induced autophagy,” Molecular and Cellular Proteomics, vol. 7, no. 12, pp. 2419–2428, 2008.
[28]
F. C. Baltanás, I. Casafont, E. Weruaga, J. R. Alonso, M. T. Berciano, and M. Lafarga, “Nucleolar disruption and cajal body disassembly are nuclear hallmarks of DNA damage-induced neurodegeneration in Purkinje cells,” Brain Pathology, vol. 21, no. 4, pp. 374–388, 2011.
[29]
V. Deretic, “Autophagy in immunity and cell-autonomous defense against intracellular microbes,” Immunological Reviews, vol. 240, no. 1, pp. 92–104, 2011.
[30]
M. Ponpuak, A. S. Davis, E. A. Roberts et al., “Delivery of cytosolic components by autophagic adaptor protein p62 endows autophagosomes with unique antimicrobial properties,” Immunity, vol. 32, no. 3, pp. 329–341, 2010.
[31]
M. F. Campagnoli, U. Ramenghi, M. Armiraglio et al., “RPS19 mutations in patients with Diamond-Blackfan anemia,” Human Mutation, vol. 29, no. 7, pp. 911–920, 2008.
[32]
I. Braakman and N. J. Bulleid, “Protein folding and modification in the mammalian endoplasmic reticulum,” Annual Review of Biochemistry, vol. 80, pp. 71–99, 2011.
[33]
T. Yorimitsu, U. Nair, Z. Yang, and D. J. Klionsky, “Endoplasmic reticulum stress triggers autophagy,” Journal of Biological Chemistry, vol. 281, no. 40, pp. 30299–30304, 2006.
[34]
K. B. Kruse, A. Dear, E. R. Kaltenbrun et al., “Mutant fibrinogen cleared from the endoplasmic reticulum via endoplasmic reticulum-associated protein degradation and autophagy: an explanation for liver disease,” American Journal of Pathology, vol. 168, no. 4, pp. 1299–1308, 2006.
[35]
K. B. Kruse, J. L. Brodsky, and A. A. McCracken, “Characterization of an ERAD gene as VPS30/ATG6 reveals two alternative and functionally distinct protein quality control pathways: one for soluble Z variant of human α-1 proteinase inhibitor (A1PiZ) and another for aggregates of A1PiZ,” Molecular Biology of the Cell, vol. 17, no. 1, pp. 203–212, 2006.
[36]
J. H. Teckman and D. H. Perlmutter, “Retention of mutant -antitrypsin Z in endoplasmic reticulum is associated with an autophagic response,” American Journal of Physiology, vol. 279, no. 5, pp. G961–G974, 2000.
[37]
E. Fujita, Y. Kouroku, A. Isoai et al., “Two endoplasmic reticulum-associated degradation (ERAD) systems for the novel variant of the mutant dysferlin: ubiquitin/proteasome ERAD(I) and autophagy/lysosome ERAD(II),” Human Molecular Genetics, vol. 16, no. 6, pp. 618–629, 2007.
[38]
K. Zhang and R. J. Kaufman, “The unfolded protein response: a stress signaling pathway critical for health and disease,” Neurology, vol. 66, no. 2, pp. S102–S109, 2006.
[39]
K. R？misch, “Endoplasmic reticulum-associated degradation,” Annual Review of Cell and Developmental Biology, vol. 21, pp. 435–456, 2005.
[40]
S. Bernales, F. R. Papa, and P. Walter, “Intracellular signaling by the unfolded protein response,” Annual Review of Cell and Developmental Biology, vol. 22, pp. 487–508, 2006.
[41]
Y. Ichimura, T. Kirisako, T. Takao et al., “A ubiquitin-like system mediates protein lipidation,” Nature, vol. 408, no. 6811, pp. 488–492, 2000.
[42]
Y. Kabeya, N. Mizushima, A. Yamamoto, S. Oshitani-Okamoto, Y. Ohsumi, and T. Yoshimori, “LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation,” Journal of Cell Science, vol. 117, no. 13, pp. 2805–2812, 2004.
[43]
W. X. Ding, H. M. Ni, W. Gao et al., “Differential effects of endoplasmic reticulum stress-induced autophagy on cell survival,” Journal of Biological Chemistry, vol. 282, no. 7, pp. 4702–4710, 2007.
[44]
Y. Kouroku, E. Fujita, I. Tanida et al., “ER stress (PERK/eIF2α phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation,” Cell Death and Differentiation, vol. 14, no. 2, pp. 230–239, 2007.
[45]
S. Bernales, K. L. McDonald, and P. Walter, “Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response.,” PLoS Biology, vol. 4, no. 12, article e423, 2006.
[46]
M. Hamasaki, T. Noda, M. Baba, and Y. Ohsumi, “Starvation triggers the delivery of the endoplasmic reticulum to the vacuole via autophagy in yeast,” Traffic, vol. 6, no. 1, pp. 56–65, 2005.
[47]
P. Salahuddint, “Genetic variants of α1-antitrypsin,” Current Protein and Peptide Science, vol. 11, no. 2, pp. 107–117, 2010.
[48]
T. Kamimoto, S. Shoji, T. Hidvegi et al., “Intracellular inclusions containing mutant -antitrypsin Z are propagated in the absence of autophagic activity,” Journal of Biological Chemistry, vol. 281, no. 7, pp. 4467–4476, 2006.
[49]
M. Baba, K. Takeshige, N. Baba, and Y. Ohsumi, “Ultrastructural analysis of the autophagic process in yeast: detection of autophagosomes and their characterization,” Journal of Cell Biology, vol. 124, no. 6, pp. 903–913, 1994.
[50]
M. J. Mazón, P. Eraso, and F. Portillo, “Efficient degradation of misfolded mutant Pma1 by endoplasmic reticulum-associated degradation requires Atg19 and the Cvt/autophagy pathway,” Molecular Microbiology, vol. 63, no. 4, pp. 1069–1077, 2007.
[51]
E. Kario, N. Amar, Z. Elazar, and A. Navon, “A new autophagy-related checkpoint in the degradation of an ERAD-M target,” Journal of Biological Chemistry, vol. 286, no. 13, pp. 11479–11491, 2011.
[52]
P. Yl？-Anttila, H. Vihinen, E. Jokitalo, and E. L. Eskelinen, “3D tomography reveals connections between the phagophore and endoplasmic reticulum,” Autophagy, vol. 5, no. 8, pp. 1180–1185, 2009.
[53]
M. Hayashi-Nishino, N. Fujita, T. Noda, A. Yamaguchi, T. Yoshimori, and A. Yamamoto, “A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation,” Nature Cell Biology, vol. 11, no. 12, pp. 1433–1437, 2009.
[54]
K. Kohno, “Stress-sensing mechanisms in the unfolded protein response: similarities and differences between yeast and mammals,” Journal of Biochemistry, vol. 147, no. 1, pp. 27–33, 2010.
[55]
T. Hanada, N. N. Noda, Y. Satomi et al., “The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy,” Journal of Biological Chemistry, vol. 282, no. 52, pp. 37298–37302, 2007.
[56]
N. Fujita, T. Itoh, H. Omori, M. Fukuda, T. Noda, and T. Yoshimori, “The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy,” Molecular Biology of the Cell, vol. 19, no. 5, pp. 2092–2100, 2008.
[57]
S. Lépine, J. C. Allegood, M. Park, P. Dent, S. Milstien, and S. Spiegel, “Sphingosine-1-phosphate phosphohydrolase-1 regulates ER stress-induced autophagy,” Cell Death and Differentiation, vol. 18, no. 2, pp. 350–361, 2011.
[58]
M. H？yer-Hansen, L. Bastholm, P. Szyniarowski et al., “Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-β, and Bcl-2,” Molecular Cell, vol. 25, no. 2, pp. 193–205, 2007.
[59]
M. H？yer-Hansen and M. J？？ttel？, “Connecting endoplasmic reticulum stress to autophagy by unfolded protein response and calcium,” Cell Death and Differentiation, vol. 14, no. 9, pp. 1576–1582, 2007.
[60]
A. L. Shaffer, M. Shapiro-Shelef, N. N. Iwakoshi et al., “XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation,” Immunity, vol. 21, no. 1, pp. 81–93, 2004.
[61]
Y. Kouroku, E. Fujita, A. Jimbo et al., “Polyglutamine aggregates stimulate ER stress signals and caspase-12 activation,” Human Molecular Genetics, vol. 11, no. 13, pp. 1505–1515, 2002.
[62]
A. Kihara, T. Noda, N. Ishihara, and Y. Ohsumi, “Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase y sorting in Saccharomyces cerevisiae,” Journal of Cell Biology, vol. 153, no. 3, pp. 519–530, 2001.
[63]
M. N. J. Seaman, E. G. Marcusson, J. L. Cereghino, and S. D. Emr, “Endosome to Golgi retrieval of the vacuolar protein sorting receptor, Vps10p, requires the function of the VPS29, VPS30, and VPS35 gene products,” Journal of Cell Biology, vol. 137, no. 1, pp. 79–92, 1997.
[64]
E. H. Baehrecke, “Autophagy: dual roles in life and death?” Nature Reviews Molecular Cell Biology, vol. 6, no. 6, pp. 505–510, 2005.
[65]
M. Ogata, S. I. Hino, A. Saito et al., “Autophagy is activated for cell survival after endoplasmic reticulum stress,” Molecular and Cellular Biology, vol. 26, no. 24, pp. 9220–9231, 2006.
