Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Neuronal Autophagy: Characteristic Features and Roles in Neuronal Pathophysiology

  • Received : 2021.01.14
  • Accepted : 2021.03.23
  • Published : 2021.11.01
Download PDF
⟨ Previous Next ⟩

Abstract

Autophagy is an important degradative pathway that eliminates misfolded proteins and damaged organelles from cells. Autophagy is crucial for neuronal homeostasis and function. A lack of or deficiency in autophagy leads to the accumulation of protein aggregates, which are associated with several neurodegenerative diseases. Compared with non-neuronal cells, neurons exhibit rapid autophagic flux because damaged organelles or protein aggregates cannot be diluted in post-mitotic cells; because of this, these cells exhibit characteristic features of autophagy, such as compartment-specific autophagy, which depends on polarized structures and rapid autophagy flux. In addition, neurons exhibit compartment-specific autophagy, which depends on polarized structures. Neuronal autophagy may have additional physiological roles other than amino acid recycling. In this review, we focus on the characteristics and regulatory factors of neuronal autophagy. We also describe intracellular selective autophagy in neurons and its association with neurodegenerative diseases.

Keywords

Acknowledgement

This research was supported by a National Research Foundation (NRF) of Korea grant funded by the Korean government (MSIT) (No. 2020R1C1C1008852) and Chung-Ang University Research Scholarship Grants in 2020.

References

  1. Adhami, F., Liao, G., Morozov, Y. M., Schloemer, A., Schmithorst, V. J., Lorenz, J. N., Dunn, R. S., Vorhees, C. V., Wills-Karp, M., Degen, J. L., Davis, R. J., Mizushima, N., Rakic, P., Dardzinski, B. J., Holland, S. K., Sharp, F. R. and Kuan, C. Y. (2006) Cerebral ischemiahypoxia induces intravascular coagulation and autophagy. Am. J. Pathol. 169, 566-583. https://doi.org/10.2353/ajpath.2006.051066
  2. Alirezaei, M., Kemball, C. C., Flynn, C. T., Wood, M. R., Whitton, J. L. and Kiosses, W. B. (2010) Short-term fasting induces profound neuronal autophagy. Autophagy 6, 702-710. https://doi.org/10.4161/auto.6.6.12376
  3. Anding, A. L. and Baehrecke, E. H. (2017) Cleaning house: selective autophagy of organelles. Dev. Cell 41, 10-22. https://doi.org/10.1016/j.devcel.2017.02.016
  4. Ariosa, A. R. and Klionsky, D. J. (2016) Autophagy core machinery: Overcoming spatial barriers in neurons. J. Mol. Med. 94, 1217-1227. https://doi.org/10.1007/s00109-016-1461-9
  5. Azarnia Tehran, D., Kuijpers, M. and Haucke, V. (2018) Presynaptic endocytic factors in autophagy and neurodegeneration. Curr. Opin. Neurobiol. 48, 153-159. https://doi.org/10.1016/j.conb.2017.12.018
  6. Bailly, Y. (2013) Autophagy - A Double-Edged Sword: Cell Survival or Death? IntechOpen, London.
  7. Ban, B. K., Jun, M. H., Ryu, H. H., Jang, D. J., Ahmad, S. T. and Lee, J. A. (2013) Autophagy negatively regulates early axon growth in cortical neurons. Mol. Cell. Biol. 33, 3907-3919. https://doi.org/10.1128/MCB.00627-13
  8. Bar-Yosef, T., Damri, O. and Agam, G. (2019) Dual role of autophagy in diseases of the central nervous system. Front. Cell. Neurosci. 13, 196. https://doi.org/10.3389/fncel.2019.00196
  9. Benito-Cuesta, I., Diez, H., Ordonez, L. and Wandosell, F. (2017) Assessment of autophagy in neurons and brain tissue. Cells 6, 25. https://doi.org/10.3390/cells6030025
  10. Berger, Z., Ravikumar, B., Menzies, F. M., Oroz, L. G., Underwood, B. R., Pangalos, M. N., Schmitt, I., Wullner, U., Evert, B. O., O'Kane, C. J. and Rubinsztein, D. C. (2006) Rapamycin alleviates toxicity of different aggregate-prone proteins. Hum. Mol. Genet. 15, 433-442. https://doi.org/10.1093/hmg/ddi458
  11. Bernard, A. and Klionsky, D. J. (2013) Autophagosome formation: tracing the source. Dev. Cell 25, 116-117. https://doi.org/10.1016/j.devcel.2013.04.004
  12. Bhaskara, R. M., Grumati, P., Garcia-Pardo, J., Kalayil, S., Covarrubias-Pinto, A., Chen, W., Kudryashev, M., Dikic, I. and Hummer, G. (2019) Curvature induction and membrane remodeling by FAM134B reticulon homology domain assist selective ER-phagy. Nat. Commun. 10, 2370. https://doi.org/10.1038/s41467-019-10345-3
  13. Binotti, B., Pavlos, N. J., Riedel, D., Wenzel, D., Vorbruggen, G., Schalk, A. M., Kuhnel, K., Boyken, J., Erck, C., Martens, H., Chua, J. J. and Jahn, R. (2015) The GTPase Rab26 links synaptic vesicles to the autophagy pathway. eLife 4, e05597. https://doi.org/10.7554/elife.05597
  14. Boland, B., Kumar, A., Lee, S., Platt, F. M., Wegiel, J., Yu, W. H. and Nixon, R. A. (2008) Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer's disease. J. Neurosci. 28, 6926-6937. https://doi.org/10.1523/JNEUROSCI.0800-08.2008
  15. Briz, V., Hsu, Y. T., Li, Y., Lee, E., Bi, X. and Baudry, M. (2013) Calpain2-mediated PTEN degradation contributes to BDNF-induced stimulation of dendritic protein synthesis. J. Neurosci. 33, 4317-4328. https://doi.org/10.1523/JNEUROSCI.4907-12.2013
  16. Carloni, S., Buonocore, G. and Balduini, W. (2008) Protective role of autophagy in neonatal hypoxia-ischemia induced brain injury. Neurobiol. Dis. 32, 329-339. https://doi.org/10.1016/j.nbd.2008.07.022
  17. Carloni, S., Girelli, S., Scopa, C., Buonocore, G., Longini, M. and Balduini, W. (2010) Activation of autophagy and Akt/CREB signaling play an equivalent role in the neuroprotective effect of rapamycin in neonatal hypoxia-ischemia. Autophagy 6, 366-377. https://doi.org/10.4161/auto.6.3.11261
  18. Carmona-Gutierrez, D., Hughes, A. L., Madeo, F. and Ruckenstuhl, C. (2016) The crucial impact of lysosomes in aging and longevity. Ageing Res. Rev. 32, 2-12. https://doi.org/10.1016/j.arr.2016.04.009
  19. Cheng, X. T., Zhou, B., Lin, M. Y., Cai, Q. and Sheng, Z. H. (2015) Axonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes. J. Cell Biol. 209, 377-386. https://doi.org/10.1083/jcb.201412046
  20. Chino, H. and Mizushima, N. (2020) ER-phagy: quality control and turnover of endoplasmic reticulum. Trends Cell Biol. 30, 384-398. https://doi.org/10.1016/j.tcb.2020.02.001
  21. Chung, W. S. and Barres, B. A. (2012) The role of glial cells in synapse elimination. Curr. Opin. Neurobiol. 22, 438-445. https://doi.org/10.1016/j.conb.2011.10.003
  22. Corrochano, S., Renna, M., Tomas-Zapico, C., Brown, S. D., Lucas, J. J., Rubinsztein, D. C. and Acevedo-Arozena, A. (2012) α-Synuclein levels affect autophagosome numbers in vivo and modulate Huntington's disease pathology. Autophagy 8, 431-432. https://doi.org/10.4161/auto.19259
  23. Corti, O., Blomgren, K., Poletti, A. and Beart, P. M. (2020) Autophagy in neurodegeneration: new insights underpinning therapy for neurological diseases. J. Neurochem. 154, 354-371. https://doi.org/10.1111/jnc.15002
  24. Deng, Z., Purtell, K., Lachance, V., Wold, M. S., Chen, S. and Yue, Z. (2017) Autophagy receptors and neurodegenerative diseases. Trends Cell Biol. 27, 491-504. https://doi.org/10.1016/j.tcb.2017.01.001
  25. Erecinska, M., Cherian, S. and Silver, I. A. (2004) Energy metabolism in mammalian brain during development. Prog. Neurobiol. 73, 397-445. https://doi.org/10.1016/j.pneurobio.2004.06.003
  26. Eskelinen, E. L. (2005) Maturation of autophagic vacuoles in mammalian cells. Autophagy 1, 1-10. https://doi.org/10.4161/auto.1.1.1270
  27. Evans, C. S. and Holzbaur, E. L. F. (2020) Quality control in neurons: mitophagy and other selective autophagy mechanisms. J. Mol. Biol. 432, 240-260. https://doi.org/10.1016/j.jmb.2019.06.031
  28. Falcon, B., Noad, J., McMahon, H., Randow, F. and Goedert, M. (2018) Galectin-8-mediated selective autophagy protects against seeded tau aggregation. J. Biol. Chem. 293, 2438-2451. https://doi.org/10.1074/jbc.m117.809293
  29. Farfel-Becker, T., Roney, J. C., Cheng, X. T., Li, S., Cuddy, S. R. and Sheng, Z. H. (2019) Neuronal soma-derived degradative lysosomes are continuously delivered to distal axons to maintain local degradation capacity. Cell Rep. 28, 51-64.e4. https://doi.org/10.1016/j.celrep.2019.06.013
  30. Farias, G. G., Guardia, C. M., Britt, D. J., Guo, X. and Bonifacino, J. S. (2015) Sorting of dendritic and axonal vesicles at the pre-axonal exclusion zone. Cell Rep. 13, 1221-1232. https://doi.org/10.1016/j.celrep.2015.09.074
  31. Fox, J. H., Connor, T., Chopra, V., Dorsey, K., Kama, J. A., Bleckmann, D., Betschart, C., Hoyer, D., Frentzel, S., Difiglia, M., Paganetti, P. and Hersch, S. M. (2010) The mTOR kinase inhibitor everolimus decreases S6 kinase phosphorylation but fails to reduce mutant huntingtin levels in brain and is not neuroprotective in the R6/2 mouse model of Huntington's disease. Mol. Neurodegener. 5, 26. https://doi.org/10.1186/1750-1326-5-26
  32. Furuta, N., Fujita, N., Noda, T., Yoshimori, T. and Amano, A. (2010) Combinational soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins VAMP8 and Vti1b mediate fusion of antimicrobial and canonical autophagosomes with lysosomes. Mol. Biol. Cell 21, 1001-1010. https://doi.org/10.1091/mbc.E09-08-0693
  33. Gabryel, B., Kost, A. and Kasprowska, D. (2012) Neuronal autophagy in cerebral ischemia--a potential target for neuroprotective strategies? Pharmacol. Rep. 64, 1-15. https://doi.org/10.1016/S1734-1140(12)70725-9
  34. Ge, P., Dawson, V. L. and Dawson, T. M. (2020) PINK1 and Parkin mitochondrial quality control: a source of regional vulnerability in Parkinson's disease. Mol. Neurodegener. 15, 20. https://doi.org/10.1186/s13024-020-00367-7
  35. Ginet, V., Puyal, J., Clarke, P. G. and Truttmann, A. C. (2009) Enhancement of autophagic flux after neonatal cerebral hypoxia-ischemia and its region-specific relationship to apoptotic mechanisms. Am. J. Pathol. 175, 1962-1974. https://doi.org/10.2353/ajpath.2009.090463
  36. Ginty, D. D. and Segal, R. A. (2002) Retrograde neurotrophin signaling: Trk-ing along the axon. Curr. Opin. Neurobiol. 12, 268-274. https://doi.org/10.1016/S0959-4388(02)00326-4
  37. Goo, M. S., Sancho, L., Slepak, N., Boassa, D., Deerinck, T. J., Ellisman, M. H., Bloodgood, B. L. and Patrick, G. N. (2017) Activity-dependent trafficking of lysosomes in dendrites and dendritic spines. J. Cell Biol. 216, 2499-2513. https://doi.org/10.1083/jcb.201704068
  38. Grishchuk, Y., Ginet, V., Truttmann, A. C., Clarke, P. G. and Puyal, J. (2011) Beclin 1-independent autophagy contributes to apoptosis in cortical neurons. Autophagy 7, 1115-1131. https://doi.org/10.4161/auto.7.10.16608
  39. Grumati, P., Dikic, I. and Stolz, A. (2018) ER-phagy at a glance. J. Cell Sci. 131, jcs217364. https://doi.org/10.1242/jcs.217364
  40. Haack, T. B., Hogarth, P., Kruer, M. C., Gregory, A., Wieland, T., Schwarzmayr, T., Graf, E., Sanford, L., Meyer, E., Kara, E., Cuno, S. M., Harik, S. I., Dandu, V. H., Nardocci, N., Zorzi, G., Dunaway, T., Tarnopolsky, M., Skinner, S., Frucht, S., Hanspal, E., Schrander-Stumpel, C., Heron, D., Mignot, C., Garavaglia, B., Bhatia, K., Hardy, J., Strom, T. M., Boddaert, N., Houlden, H. H., Kurian, M. A., Meitinger, T., Prokisch, H. and Hayflick, S. J. (2012) Exome sequencing reveals de novo WDR45 mutations causing a phenotypically distinct, X-linked dominant form of NBIA. Am. J. Hum. Genet. 91, 1144-1149. https://doi.org/10.1016/j.ajhg.2012.10.019
  41. Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H. and Mizushima, N. (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441, 885-889. https://doi.org/10.1038/nature04724
  42. Hernandez, D., Torres, C. A., Setlik, W., Cebrian, C., Mosharov, E. V., Tang, G., Cheng, H. C., Kholodilov, N., Yarygina, O., Burke, R. E., Gershon, M. and Sulzer, D. (2012) Regulation of presynaptic neurotransmission by macroautophagy. Neuron 74, 277-284. https://doi.org/10.1016/j.neuron.2012.02.020
  43. Hill, S. E. and Colon-Ramos, D. A. (2020) The journey of the synaptic autophagosome: a cell biological perspective. Neuron 105, 961-973. https://doi.org/10.1016/j.neuron.2020.01.018
  44. Hoffmann-Conaway, S., Brockmann, M. M., Schneider, K., Annamneedi, A., Rahman, K. A., Bruns, C., Textoris-Taube, K., Trimbuch, T., Smalla, K. H., Rosenmund, C., Gundelfinger, E. D., Garner, C. C. and Montenegro-Venegas, C. (2020) Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice. eLife 9, e56590. https://doi.org/10.7554/elife.56590
  45. Hoffmann, S., Orlando, M., Andrzejak, E., Bruns, C., Trimbuch, T., Rosenmund, C., Garner, C. C. and Ackermann, F. (2019) LightActivated ROS production induces synaptic autophagy. J. Neurosci. 39, 2163-2183. https://doi.org/10.1523/JNEUROSCI.1317-18.2019
  46. Hori, I., Otomo, T., Nakashima, M., Miya, F., Negishi, Y., Shiraishi, H., Nonoda, Y., Magara, S., Tohyama, J., Okamoto, N., Kumagai, T., Shimoda, K., Yukitake, Y., Kajikawa, D., Morio, T., Hattori, A., Nakagawa, M., Ando, N., Nishino, I., Kato, M., Tsunoda, T., Saitsu, H., Kanemura, Y., Yamasaki, M., Kosaki, K., Matsumoto, N., Yoshimori, T. and Saitoh, S. (2017) Defects in autophagosome-lysosome fusion underlie Vici syndrome, a neurodevelopmental disorder with multisystem involvement. Sci. Rep. 7, 3552. https://doi.org/10.1038/s41598-017-02840-8
  47. Jiang, X., Litkowski, P. E., Taylor, A. A., Lin, Y., Snider, B. J. and Moulder, K. L. (2010) A role for the ubiquitin-proteasome system in activity-dependent presynaptic silencing. J. Neurosci. 30, 1798-1809. https://doi.org/10.1523/JNEUROSCI.4965-09.2010
  48. Joselin, A. P., Hewitt, S. J., Callaghan, S. M., Kim, R. H., Chung, Y. H., Mak, T. W., Shen, J., Slack, R. S. and Park, D. S. (2012) ROS-dependent regulation of Parkin and DJ-1 localization during oxidative stress in neurons. Hum. Mol. Genet. 21, 4888-4903. https://doi.org/10.1093/hmg/dds325
  49. Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y. and Yoshimori, T. (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 19, 5720-5728. https://doi.org/10.1093/emboj/19.21.5720
  50. Katsumata, K., Nishiyama, J., Inoue, T., Mizushima, N., Takeda, J. and Yuzaki, M. (2010) Dynein- and activity-dependent retrograde transport of autophagosomes in neuronal axons. Autophagy 6, 378-385. https://doi.org/10.4161/auto.6.3.11262
  51. Koike, M., Shibata, M., Tadakoshi, M., Gotoh, K., Komatsu, M., Waguri, S., Kawahara, N., Kuida, K., Nagata, S., Kominami, E., Tanaka, K. and Uchiyama, Y. (2008) Inhibition of autophagy prevents hippocampal pyramidal neuron death after hypoxic-ischemic injury. Am. J. Pathol. 172, 454-469. https://doi.org/10.2353/ajpath.2008.070876
  52. Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E. and Tanaka, K. (2006) Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441, 880-884. https://doi.org/10.1038/nature04723
  53. Kononenko, N. L., Classen, G. A., Kuijpers, M., Puchkov, D., Maritzen, T., Tempes, A., Malik, A. R., Skalecka, A., Bera, S., Jaworski, J. and Haucke, V. (2017) Retrograde transport of TrkB-containing autophagosomes via the adaptor AP-2 mediates neuronal complexity and prevents neurodegeneration. Nat. Commun. 8, 14819. https://doi.org/10.1038/ncomms14819
  54. Koyano, F., Okatsu, K., Kosako, H., Tamura, Y., Go, E., Kimura, M., Kimura, Y., Tsuchiya, H., Yoshihara, H., Hirokawa, T., Endo, T., Fon, E. A., Trempe, J. F., Saeki, Y., Tanaka, K. and Matsuda, N. (2014) Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature 510, 162-166. https://doi.org/10.1038/nature13392
  55. Ktistakis, N. T. and Tooze, S. A. (2016) Digesting the expanding mechanisms of autophagy. Trends Cell Biol. 26, 624-635. https://doi.org/10.1016/j.tcb.2016.03.006
  56. Kuijpers, M., Kochlamazashvili, G., Stumpf, A., Puchkov, D., Swaminathan, A., Lucht, M. T., Krause, E., Maritzen, T., Schmitz, D. and Haucke, V. (2020) Neuronal autophagy regulates presynaptic neurotransmission by controlling the axonal endoplasmic reticulum. Neuron 109, 299-313.
  57. Kulkarni, A., Chen, J. and Maday, S. (2018) Neuronal autophagy and intercellular regulation of homeostasis in the brain. Curr. Opin. Nuerobiol. 51, 29-36. https://doi.org/10.1016/j.conb.2018.02.008
  58. Kulkarni, V. V. and Maday, S. (2018) Neuronal endosomes to lysosomes: a journey to the soma. J. Cell Biol. 217, 2977-2979. https://doi.org/10.1083/jcb.201806139
  59. Kurashige, T., Kuramochi, M., Ohsawa, R., Yamashita, Y., Shioi, G., Morino, H., Kamada, M., Ayaki, T., Ito, H., Sotomaru, Y., Maruyama, H. and Kawakami, H. (2020) Optineurin defects cause TDP43-pathology with autophagic vacuolar formation. Neurobiol. Dis. 148, 105215.
  60. Kurth, I., Pamminger, T., Hennings, J. C., Soehendra, D., Huebner, A. K., Rotthier, A., Baets, J., Senderek, J., Topaloglu, H., Farrell, S. A., Nurnberg, G., Nurnberg, P., De Jonghe, P., Gal, A., Kaether, C., Timmerman, V. and Hubner, C. A. (2009) Mutations in FAM134B, encoding a newly identified Golgi protein, cause severe sensory and autonomic neuropathy. Nat. Genet. 41, 1179-1181. https://doi.org/10.1038/ng.464
  61. Lee, K. M., Hwang, S. K. and Lee, J. A. (2013) Neuronal autophagy and neurodevelopmental disorders. Exp. Neurobiol. 22, 133-142. https://doi.org/10.5607/en.2013.22.3.133
  62. Lee, S., Sato, Y. and Nixon, R. A. (2011) Primary lysosomal dysfunction causes cargo-specific deficits of axonal transport leading to Alzheimer-like neuritic dystrophy. Autophagy 7, 1562-1563. https://doi.org/10.4161/auto.7.12.17956
  63. Lee, S. H., Simonetta, A. and Sheng, M. (2004) Subunit rules governing the sorting of internalized AMPA receptors in hippocampal neurons. Neuron 43, 221-236. https://doi.org/10.1016/j.neuron.2004.06.015
  64. Liang, Y. and Sigrist, S. (2018) Autophagy and proteostasis in the control of synapse aging and disease. Curr. Opin. Nuerobiol. 48, 113-121. https://doi.org/10.1016/j.conb.2017.12.006
  65. Lim, J., Kim, H. W., Youdim, M. B., Rhyu, I. J., Choe, K. M. and Oh, Y. J. (2011) Binding preference of p62 towards LC3-ll during dopaminergic neurotoxin-induced impairment of autophagic flux. Autophagy 7, 51-60. https://doi.org/10.4161/auto.7.1.13909
  66. Loeffler, D. A. (2019) Influence of normal aging on brain autophagy: a complex scenario. Front. Aging Neurosci. 11, 49. https://doi.org/10.3389/fnagi.2019.00049
  67. Luningschror, P., Binotti, B., Dombert, B., Heimann, P., Perez-Lara, A., Slotta, C., Thau-Habermann, N., von Collenberg, C. R., Karl, F., Damme, M., Horowitz, A., Maystadt, I., Fuchtbauer, A., Fuchtbauer, E. M., Jablonka, S., Blum, R., Uceyler, N., Petri, S., Kaltschmidt, B., Jahn, R., Kaltschmidt, C. and Sendtner, M. (2017) Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease. Nat. Commun. 8, 678. https://doi.org/10.1038/s41467-017-00689-z
  68. Maday, S. and Holzbaur, E. L. (2014) Autophagosome biogenesis in primary neurons follows an ordered and spatially regulated pathway. Dev. Cell 30, 71-85. https://doi.org/10.1016/j.devcel.2014.06.001
  69. Maday, S. and Holzbaur, E. L. (2016) Compartment-specific regulation of autophagy in primary neurons. J. Neurosci. 36, 5933-5945. https://doi.org/10.1523/JNEUROSCI.4401-15.2016
  70. Maiuri, M. C., Zalckvar, E., Kimchi, A. and Kroemer, G. (2007) Selfeating and self-killing: crosstalk between autophagy and apoptosis. Nat. Rev. Mol. Cell Biol. 8, 741-752. https://doi.org/10.1038/nrm2239
  71. Martinez-Vicente, M. (2017) Neuronal mitophagy in neurodegenerative diseases. Front. Mol. Neurosci. 10, 64. https://doi.org/10.3389/fnmol.2017.00064
  72. Mazure, N. M. and Pouyssegur, J. (2010) Hypoxia-induced autophagy: cell death or cell survival? Curr. Opin. Cell Biol. 22, 177-180. https://doi.org/10.1016/j.ceb.2009.11.015
  73. McEwan, D. G. and Dikic, I. (2011) The three musketeers of autophagy: phosphorylation, ubiquitylation and acetylation. Trends Cell Biol. 21, 195-201. https://doi.org/10.1016/j.tcb.2010.12.006
  74. Metcalf, D. J., Garcia-Arencibia, M., Hochfeld, W. E. and Rubinsztein, D. C. (2012) Autophagy and misfolded proteins in neurodegeneration. Exp. Neurol. 238, 22-28. https://doi.org/10.1016/j.expneurol.2010.11.003
  75. Mitra, S., Tsvetkov, A. S. and Finkbeiner, S. (2009) Protein turnover and inclusion body formation. Autophagy 5, 1037-1038. https://doi.org/10.4161/auto.5.7.9291
  76. Mizushima, N., Yamamoto, A., Matsui, M., Yoshimori, T. and Ohsumi, Y. (2004) In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol. Biol. Cell 15, 1101-1111. https://doi.org/10.1091/mbc.E03-09-0704
  77. Mollereau, B. and Walter, L. (2019) Is WDR45 the missing link for ER stress-induced autophagy in beta-propeller associated neurodegeneration? Autophagy 15, 2163-2164. https://doi.org/10.1080/15548627.2019.1668229
  78. Moore, A. S. and Holzbaur, E. L. (2016) Dynamic recruitment and activation of ALS-associated TBK1 with its target optineurin are required for efficient mitophagy. Proc. Natl. Acad. Sci. U.S.A. 113, E3349-E3358.
  79. Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., Bruce, J., Schuck, T., Grossman, M., Clark, C. M., McCluskey, L. F., Miller, B. L., Masliah, E., Mackenzie, I. R., Feldman, H., Feiden, W., Kretzschmar, H. A., Trojanowski, J. Q. and Lee, V. M. (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130-133. https://doi.org/10.1126/science.1134108
  80. Nicholls, D. G. and Budd, S. L. (2000) Mitochondria and neuronal survival. Physiol. Rev. 80, 315-360. https://doi.org/10.1152/physrev.2000.80.1.315
  81. Nikoletopoulou, V., Papandreou, M. E. and Tavernarakis, N. (2015) Autophagy in the physiology and pathology of the central nervous system. Cell Death Differ. 22, 398-407. https://doi.org/10.1038/cdd.2014.204
  82. Nikoletopoulou, V., Sidiropoulou, K., Kallergi, E., Dalezios, Y. and Tavernarakis, N. (2017) Modulation of autophagy by BDNF underlies synaptic plasticity. Cell Metab. 26, 230-242.e5. https://doi.org/10.1016/j.cmet.2017.06.005
  83. Nixon, R. A., Wegiel, J., Kumar, A., Yu, W. H., Peterhoff, C., Cataldo, A. and Cuervo, A. M. (2005) Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. J. Neuropathol. Exp. Neurol. 64, 113-122. https://doi.org/10.1093/jnen/64.2.113
  84. Ohba, C., Nabatame, S., Iijima, Y., Nishiyama, K., Tsurusaki, Y., Nakashima, M., Miyake, N., Tanaka, F., Ozono, K., Saitsu, H. and Matsumoto, N. (2014) De novo WDR45 mutation in a patient showing clinically Rett syndrome with childhood iron deposition in brain. J. Hum. Genet. 59, 292-295. https://doi.org/10.1038/jhg.2014.18
  85. Okerlund, N. D., Schneider, K., Leal-Ortiz, S., Montenegro-Venegas, C., Kim, S. A., Garner, L. C., Waites, C. L., Gundelfinger, E. D., Reimer, R. J. and Garner, C. C. (2017) Bassoon controls presynaptic autophagy through Atg5. Neuron 93, 897-913.e7. https://doi.org/10.1016/j.neuron.2017.01.026
  86. Padamsey, Z., McGuinness, L., Bardo, S. J., Reinhart, M., Tong, R., Hedegaard, A., Hart, M. L. and Emptage, N. J. (2017) Activity-dependent exocytosis of lysosomes regulates the structural plasticity of dendritic spines. Neuron 93, 132-146. https://doi.org/10.1016/j.neuron.2016.11.013
  87. Philippidou, P., Valdez, G., Akmentin, W., Bowers, W. J., Federoff, H. J. and Halegoua, S. (2011) Trk retrograde signaling requires persistent, Pincher-directed endosomes. Proc. Natl. Acad. Sci. U.S.A. 108, 852-857. https://doi.org/10.1073/pnas.1015981108
  88. Puyal, J., Vaslin, A., Mottier, V. and Clarke, P. G. (2009) Postischemic treatment of neonatal cerebral ischemia should target autophagy. Ann. Neurol. 66, 378-389. https://doi.org/10.1002/ana.21714
  89. Ramesh Babu, J., Lamar Seibenhener, M., Peng, J., Strom, A. L., Kemppainen, R., Cox, N., Zhu, H., Wooten, M. C., Diaz-Meco, M. T., Moscat, J. and Wooten, M. W. (2008) Genetic inactivation of p62 leads to accumulation of hyperphosphorylated tau and neurodegeneration. J. Neurochem. 106, 107-120. https://doi.org/10.1111/j.1471-4159.2008.05340.x
  90. Rami, A., Langhagen, A. and Steiger, S. (2008) Focal cerebral ischemia induces upregulation of Beclin 1 and autophagy-like cell death. Neurobiol. Dis. 29, 132-141. https://doi.org/10.1016/j.nbd.2007.08.005
  91. Reichardt, L. F. (2006) Neurotrophin-regulated signalling pathways. Philos. Trans. R. Soc. Lond. B Biol. Sci. 361, 1545-1564. https://doi.org/10.1098/rstb.2006.1894
  92. Richter, B., Sliter, D. A., Herhaus, L., Stolz, A., Wang, C., Beli, P., Zaffagnini, G., Wild, P., Martens, S., Wagner, S. A., Youle, R. J. and Dikic, I. (2016) Phosphorylation of OPTN by TBK1 enhances its binding to Ub chains and promotes selective autophagy of damaged mitochondria. Proc. Natl. Acad. Sci. U.S.A. 113, 4039-4044. https://doi.org/10.1073/pnas.1523926113
  93. Saito, T. and Sadoshima, J. (2015) Molecular mechanisms of mitochondrial autophagy/mitophagy in the heart. Circ. Res. 116, 1477-1490. https://doi.org/10.1161/CIRCRESAHA.116.303790
  94. Schwarz, L. A., Hall, B. J. and Patrick, G. N. (2010) Activity-dependent ubiquitination of GluA1 mediates a distinct AMPA receptor endocytosis and sorting pathway. J. Neurosci. 30, 16718-16729. https://doi.org/10.1523/JNEUROSCI.3686-10.2010
  95. Sharma, A., Hoeffer, C. A., Takayasu, Y., Miyawaki, T., McBride, S. M., Klann, E. and Zukin, R. S. (2010) Dysregulation of mTOR signaling in fragile X syndrome. J. Neurosci. 30, 694-702. https://doi.org/10.1523/JNEUROSCI.3696-09.2010
  96. Shehata, M., Matsumura, H., Okubo-Suzuki, R., Ohkawa, N. and Inokuchi, K. (2012) Neuronal stimulation induces autophagy in hippocampal neurons that is involved in AMPA receptor degradation after chemical long-term depression. J. Neurosci. 32, 10413-10422. https://doi.org/10.1523/JNEUROSCI.4533-11.2012
  97. Shen, W. and Ganetzky, B. (2009) Autophagy promotes synapse development in Drosophila. J. Cell Biol. 187, 71-79. https://doi.org/10.1083/jcb.200907109
  98. Sheng, R. and Qin, Z. H. (2015) The divergent roles of autophagy in ischemia and preconditioning. Acta Pharmacol. Sin. 36, 411-420. https://doi.org/10.1038/aps.2014.151
  99. Shibata, M., Lu, T., Furuya, T., Degterev, A., Mizushima, N., Yoshimori, T., MacDonald, M., Yankner, B. and Yuan, J. (2006) Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1. J. Biol. Chem. 281, 14474-14485. https://doi.org/10.1074/jbc.M600364200
  100. Smith, E. D., Prieto, G. A., Tong, L., Sears-Kraxberger, I., Rice, J. D., Steward, O. and Cotman, C. W. (2014) Rapamycin and interleukin1beta impair brain-derived neurotrophic factor-dependent neuron survival by modulating autophagy. J. Biol. Chem. 289, 20615-20629. https://doi.org/10.1074/jbc.M114.568659
  101. Son, J. H., Shim, J. H., Kim, K. H., Ha, J. Y. and Han, J. Y. (2012) Neuronal autophagy and neurodegenerative diseases. Exp. Mol. Med. 44, 89-98. https://doi.org/10.3858/emm.2012.44.2.031
  102. Song, A. H., Wang, D., Chen, G., Li, Y., Luo, J., Duan, S. and Poo, M. M. (2009) A selective filter for cytoplasmic transport at the axon initial segment. Cell 136, 1148-1160. https://doi.org/10.1016/j.cell.2009.01.016
  103. Soukup, S. F., Kuenen, S., Vanhauwaert, R., Manetsberger, J., Hernandez-Diaz, S., Swerts, J., Schoovaerts, N., Vilain, S., Gounko, N. V., Vints, K., Geens, A., De Strooper, B. and Verstreken, P. (2016) A LRRK2-dependent endophilinA phosphoswitch is critical for macroautophagy at presynaptic terminals. Neuron 92, 829-844. https://doi.org/10.1016/j.neuron.2016.09.037
  104. Stavoe, A. K., Hill, S. E., Hall, D. H. and Colon-Ramos, D. A. (2016) KIF1A/UNC-104 transports ATG-9 to regulate neurodevelopment and autophagy at synapses. Dev. Cell 38, 171-185. https://doi.org/10.1016/j.devcel.2016.06.012
  105. Stephan, A. H., Barres, B. A. and Stevens, B. (2012) The complement system: an unexpected role in synaptic pruning during development and disease. Annu. Rev. Neurosci. 35, 369-389. https://doi.org/10.1146/annurev-neuro-061010-113810
  106. Suzuki, K., Kubota, Y., Sekito, T. and Ohsumi, Y. (2007) Hierarchy of Atg proteins in pre-autophagosomal structure organization. Genes Cells 12, 209-218. https://doi.org/10.1111/j.1365-2443.2007.01050.x
  107. Tang, G., Gudsnuk, K., Kuo, S. H., Cotrina, M. L., Rosoklija, G., Sosunov, A., Sonders, M. S., Kanter, E., Castagna, C., Yamamoto, A., Yue, Z., Arancio, O., Peterson, B. S., Champagne, F., Dwork, A. J., Goldman, J. and Sulzer, D. (2014) Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits. Neuron 83, 1131-1143. https://doi.org/10.1016/j.neuron.2014.07.040
  108. Tsuyuki, S., Takabayashi, M., Kawazu, M., Kudo, K., Watanabe, A., Nagata, Y., Kusama, Y. and Yoshida, K. (2014) Detection of WIPI1 mRNA as an indicator of autophagosome formation. Autophagy 10, 497-513. https://doi.org/10.4161/auto.27419
  109. Tsvetkov, A. S., Miller, J., Arrasate, M., Wong, J. S., Pleiss, M. A. and Finkbeiner, S. (2010) A small-molecule scaffold induces autophagy in primary neurons and protects against toxicity in a Huntington disease model. Proc. Natl. Acad. Sci. U.S.A. 107, 16982-16987. https://doi.org/10.1073/pnas.1004498107
  110. Turco, E., Witt, M., Abert, C., Bock-Bierbaum, T., Su, M. Y., Trapannone, R., Sztacho, M., Danieli, A., Shi, X., Zaffagnini, G., Gamper, A., Schuschnig, M., Fracchiolla, D., Bernklau, D., Romanov, J., Hartl, M., Hurley, J. H., Daumke, O. and Martens, S. (2019) FIP200 claw domain binding to p62 promotes autophagosome formation at ubiquitin condensates. Mol. Cell 74, 330-346.e11. https://doi.org/10.1016/j.molcel.2019.01.035
  111. Van Laar, V. S., Roy, N., Liu, A., Rajprohat, S., Arnold, B., Dukes, A. A., Holbein, C. D. and Berman, S. B. (2015) Glutamate excitotoxicity in neurons triggers mitochondrial and endoplasmic reticulum accumulation of Parkin, and, in the presence of N-acetyl cysteine, mitophagy. Neurobiol. Dis. 74, 180-193. https://doi.org/10.1016/j.nbd.2014.11.015
  112. Vanhauwaert, R., Kuenen, S., Masius, R., Bademosi, A., Manetsberger, J., Schoovaerts, N., Bounti, L., Gontcharenko, S., Swerts, J., Vilain, S., Picillo, M., Barone, P., Munshi, S. T., de Vrij, F. M., Kushner, S. A., Gounko, N. V., Mandemakers, W., Bonifati, V., Meunier, F. A., Soukup, S. F. and Verstreken, P. (2017) The SAC1 domain in synaptojanin is required for autophagosome maturation at presynaptic terminals. EMBO J. 36, 1392-1411. https://doi.org/10.15252/embj.201695773
  113. Vijayan, V. and Verstreken, P. (2017) Autophagy in the presynaptic compartment in health and disease. J. Cell Biol. 216, 1895-1906. https://doi.org/10.1083/jcb.201611113
  114. Wallings, R. L., Humble, S. W., Ward, M. E. and Wade-Martins, R. (2019) Lysosomal dysfunction at the centre of parkinson's disease and frontotemporal dementia/amyotrophic lateral sclerosis. Trends Neurosci. 42, 899-912. https://doi.org/10.1016/j.tins.2019.10.002
  115. Wan, H., Wang, Q., Chen, X., Zeng, Q., Shao, Y., Fang, H., Liao, X., Li, H. S., Liu, M. G., Xu, T. L., Diao, M., Li, D., Meng, B., Tang, B., Zhang, Z. and Liao, L. (2020) WDR45 contributes to neurodegeneration through regulation of ER homeostasis and neuronal death. Autophagy 16, 531-547. https://doi.org/10.1080/15548627.2019.1630224
  116. Wang, D. B., Kinoshita, Y., Kinoshita, C., Uo, T., Sopher, B. L., Cudaback, E., Keene, C. D., Bilousova, T., Gylys, K., Case, A., Jayadev, S., Wang, H. G., Garden, G. A. and Morrison, R. S. (2015a) Loss of endophilin-B1 exacerbates Alzheimer's disease pathology. Brain 138, 2005-2019. https://doi.org/10.1093/brain/awv128
  117. Wang, M. M., Feng, Y. S., Yang, S. D., Xing, Y., Zhang, J., Dong, F. and Zhang, F. (2019) The relationship between autophagy and brain plasticity in neurological diseases. Front. Cell. Neurosci. 13, 228. https://doi.org/10.3389/fncel.2019.00228
  118. Wang, T., Martin, S., Papadopulos, A., Harper, C. B., Mavlyutov, T. A., Niranjan, D., Glass, N. R., Cooper-White, J. J., Sibarita, J. B., Choquet, D., Davletov, B. and Meunier, F. A. (2015b) Control of autophagosome axonal retrograde flux by presynaptic activity unveiled using botulinum neurotoxin type A. J. Neurosci. 35, 6179-6194. https://doi.org/10.1523/JNEUROSCI.3757-14.2015
  119. Watanabe, S., Mamer, L. E., Raychaudhuri, S., Luvsanjav, D., Eisen, J., Trimbuch, T., Sohl-Kielczynski, B., Fenske, P., Milosevic, I., Rosenmund, C. and Jorgensen, E. M. (2018) Synaptojanin and endophilin mediate neck formation during ultrafast endocytosis. Neuron 98, 1184-1197.e6. https://doi.org/10.1016/j.neuron.2018.06.005
  120. Wen, Y. D., Sheng, R., Zhang, L. S., Han, R., Zhang, X., Zhang, X. D., Han, F., Fukunaga, K. and Qin, Z. H. (2008) Neuronal injury in rat model of permanent focal cerebral ischemia is associated with activation of autophagic and lysosomal pathways. Autophagy 4, 762-769. https://doi.org/10.4161/auto.6412
  121. Wild, P., McEwan, D. G. and Dikic, I. (2014) The LC3 interactome at a glance. J. Cell Sci. 127, 3-9. https://doi.org/10.1242/jcs.140426
  122. Williams, A., Jahreiss, L., Sarkar, S., Saiki, S., Menzies, F. M., Ravikumar, B. and Rubinsztein, D. C. (2006) Aggregate-prone proteins are cleared from the cytosol by autophagy: therapeutic implications. Curr. Top. Dev. Biol. 76, 89-101. https://doi.org/10.1016/S0070-2153(06)76003-3
  123. Winden, K. D., Ebrahimi-Fakhari, D. and Sahin, M. (2018) Abnormal mTOR activation in autism. Annu. Rev. Neurosci. 41, 1-23. https://doi.org/10.1146/annurev-neuro-080317-061747
  124. Wong, Y. C. and Holzbaur, E. L. (2014) Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagythat is disrupted by an ALS-linked mutation. Proc. Natl. Acad. Sci. U.S.A. 111, E4439- E4448.
  125. Wurzer, B., Zaffagnini, G., Fracchiolla, D., Turco, E., Abert, C., Romanov, J. and Martens, S. (2015) Oligomerization of p62 allows for selection of ubiquitinated cargo and isolation membrane during selective autophagy. eLife 4, e08941. https://doi.org/10.7554/elife.08941
  126. Xie, Z. and Klionsky, D. J. (2007) Autophagosome formation: core machinery and adaptations. Nat. Cell Biol. 9, 1102-1109.
  127. Yamamoto, A. and Yue, Z. (2014) Autophagy and its normal and pathogenic states in the brain. Annu. Rev. Neurosci. 37, 55-78. https://doi.org/10.1146/annurev-neuro-071013-014149
  128. Yan, J., Porch, M. W., Court-Vazquez, B., Bennett, M. V. L. and Zukin, R. S. (2018) Activation of autophagy rescues synaptic and cognitive deficits in fragile X mice. Proc. Natl. Acad. Sci. U.S.A. 115, E9707-E9716.
  129. Yap, C. C., Digilio, L., McMahon, L. P., Garcia, A. D. R. and Winckler, B. (2018) Degradation of dendritic cargos requires Rab7-dependent transport to somatic lysosomes. J. Cell Biol. 217, 3141-3159. https://doi.org/10.1083/jcb.201711039
  130. Yoshimori, T., Yamamoto, A., Moriyama, Y., Futai, M. and Tashiro, Y. (1991) Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, inhibits acidification and protein degradation in lysosomes of cultured cells. J. Biol. Chem. 266, 17707-17712. https://doi.org/10.1016/S0021-9258(19)47429-2
  131. Young, J. E., Martinez, R. A. and La Spada, A. R. (2009) Nutrient deprivation induces neuronal autophagy and implicates reduced insulin signaling in neuroprotective autophagy activation. J. Biol. Chem. 284, 2363-2373. https://doi.org/10.1074/jbc.M806088200
  132. Zatyka, M., Sarkar, S. and Barrett, T. (2020) Autophagy in rare (non-lysosomal) neurodegenerative diseases. J. Mol. Biol. 432, 2735-2753. https://doi.org/10.1016/j.jmb.2020.02.012
  133. Zhu, C., Wang, X., Xu, F., Bahr, B. A., Shibata, M., Uchiyama, Y., Hagberg, H. and Blomgren, K. (2005) The influence of age on apoptotic and other mechanisms of cell death after cerebral hypoxia-ischemia. Cell Death Differ. 12, 162-176. https://doi.org/10.1038/sj.cdd.4401545
  134. Zhu, Z., Yang, C., Iyaswamy, A., Krishnamoorthi, S., Sreenivasmurthy, S. G., Liu, J., Wang, Z., Tong, B. C., Song, J., Lu, J., Cheung, K. H. and Li, M. (2019) Balancing mTOR signaling and autophagy in the treatment of Parkinson's disease. Int. J. Mol. Sci. 20, 728. https://doi.org/10.3390/ijms20030728
  135. Zolkipli-Cunningham, Z. and Falk, M. J. (2017) Clinical effects of chemical exposures on mitochondrial function. Toxicology 391, 90-99. https://doi.org/10.1016/j.tox.2017.07.009

Cited by

  1. The Function of KDEL Receptors as UPR Genes in Disease vol.22, pp.11, 2021, https://doi.org/10.3390/ijms22115436
  2. Curcumin induces autophagic cell death in human thyroid cancer cells vol.78, 2022, https://doi.org/10.1016/j.tiv.2021.105254