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Autophagosomes initiate distally and mature during transport toward the cell soma in primary neurons
Open accessAbstract
Autophagy is an essential cellular degradation pathway in neurons; defects in autophagy are sufficient to induce neurodegeneration. In this paper, we investigate autophagosome dynamics in primary dorsal root ganglion neurons. Autophagosome biogenesis occurs distally in a constitutive process at the neurite tip. Autophagosomes initially move bidirectionally and then switch to unidirectional, processive movement toward the cell soma driven by dynein. Autophagosomes copurify with anterograde and retrograde motors, suggesting that the activity of bound kinesin motors is effectively down-regulated to yield robust retrograde motility driven by dynein. Both organelle and soluble cargoes are internalized into autophagosomes, including mitochondria and ubiquitin. As autophagosomes move distally to proximally, they undergo maturation and become increasingly acidified, consistent with the formation of an autolysosomal compartment that may more efficiently degrade cargo. This maturation is accompanied by a switch to bidirectional motility characteristic of lysosomes. Together, autophagosome biogenesis and maturation in primary neurons is a constitutive process that is spatially and temporally regulated along the axon.
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“Lysosomes fuse with autophagosome in the distal axon, and they mature on the way back to the soma (Maday et al., 2012).”
From TMEM55B promotes anterograde transport and distal axonal distribution of LAMP1-positive organelles (2026) · cites this paper as Maday et al., 2012
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Autophagosome trafficking along axons was recently described.31”
From Measurement of autophagy flux in the nervous system in vivo (2013) · cites this paper as [31]
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In the citing paper
“Remarkably, the velocities obtained were in the same order of magnitude to the ones recently reported for autophagosomes in axons of DRGs obtained from LC3-GFP transgenic mice.31”
From Measurement of autophagy flux in the nervous system in vivo (2013) · cites this paper as [31]
In the citing paper
“Newly-formed autophagosomes in neuronal processes undergo retrograde transport to the soma and proximal segments of neurites to fuse with somatodendritic lysosomes for cargo degradation, with maturation and acidification of the autophagosomal lumen developing en passant [370,372,374].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [372]
In the citing paper
“Autophagy initiation typically begins outside of the soma, in the distal axon tip [370,372,373].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [372]
In the citing paper
“Bidirectional movements have been reported for a variety of organelles and vesicles (Welte, 2004), including even those that move persistently in one direction, such as mitochondria (Saxton and Hollenbeck, 2012), autophagosomes (Maday et al., 2012), and vesicles (Encalada et al., 2011), as they undergo axonal transport.”
From Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis (2015) · cites this paper as Maday et al., 2012
In the citing paper
“puncta may be numerous in neurites, especially within dystrophic swellings and, in many cases, these vacuoles are amphisomes or autolysosomes, reflecting the delayed or inhibited degradation of LC3 despite the presence of abundant hydrolase activity [77,84].”
From Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1 (2021) · cites this paper as [84]
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Citations
Cites
Autophagy fights disease through cellular self-digestion
Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J. (2008) · Nature · doi:10.1038/nature06639 · Cited by 6,452
Pankiv, S., Clausen, T. H., Lamark, T., Brech, A., Bruun, J.-A., Outzen, H., Øvervatn, A., Bjørkøy, G., & Johansen, T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702824200 · Cited by 4,578
Motor Neuron Degeneration in Mice that Express a Human Cu,Zn Superoxide Dismutase Mutation
Gurney, M. E., Pu, H., Chiu, A. Y., Dal Canto, M. C., Polchow, C. Y., Alexander, D. D., Caliendo, J., Hentati, A., Kwon, Y. W., Deng, H.-X., et al. (1994) · Science · doi:10.1126/science.8209258 · Cited by 4,143
Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
Narendra, D., Tanaka, A., Suen, D.-F., & Youle, R. J. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200809125 · Cited by 4,026
Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., et al. (2006) · Nature · doi:10.1038/nature04724 · Cited by 3,882
Loss of autophagy in the central nervous system causes neurodegeneration in mice
Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J.-I., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., et al. (2006) · Nature · doi:10.1038/nature04723 · Cited by 3,500
Autophagosome formation: core machinery and adaptations
Xie, Z., & Klionsky, D. J. (2007) · Nature Cell Biology · doi:10.1038/ncb1007-1102 · Cited by 2,237
Mizushima, N., Yamamoto, A., Matsui, M., Yoshimori, T., & Ohsumi, Y. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e03-09-0704 · Cited by 2,105
Mitochondria Supply Membranes for Autophagosome Biogenesis during Starvation
Hailey, D. W., Rambold, A. S., Satpute‐Krishnan, P., Mitra, K., Sougrat, R., Kim, P. K., & Lippincott‐Schwartz, J. (2010) · Cell · doi:10.1016/j.cell.2010.04.009 · Cited by 1,491
A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation
Hayashi-Nishino, M., Fujita, N., Noda, T., Yamaguchi, A., Yoshimori, T., & Yamamoto, A. (2009) · Nature Cell Biology · doi:10.1038/ncb1991 · Cited by 1,083
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The Dynamic Localization of Cytoplasmic Dynein in Neurons Is Driven by Kinesin-1
Twelvetrees, A. E., Pernigo, S., Sanger, A., Guedes-Dias, P., Schiavo, G., Steiner, R. A., Dodding, M. P., & Holzbaur, E. L. F. (2016) · Neuron · doi:10.1016/j.neuron.2016.04.046 · Cited by 122
“Dynein is essential for many axonal functions including: growth cone extension (Grabham et al., 2007; Myers et al., 2006); axon elongation (Roossien et al., 2014); retrograde neurotrophic signaling (Heerssen et al., 2004; Yano et al., 2001); and autophagy (Maday et al., 2012).”
Self-citationMitochondrial dynamics and quality control in Huntington's disease
Guedes-Dias, P., Pinho, B. R., Soares, T. R., de Proença, J., Duchen, M. R., & Oliveira, J. M. A. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.09.008 · Cited by 119
“Neuronal autophagosomes are generated distally and display robust retrograde movement along the axon towards the soma, where most cargo degradation likely takes place (Lee et al., 2011; Maday and Holzbaur, 2014; Maday et al., 2012).”
BackgroundAutophagosome dynamics in neurodegeneration at a glance
Wong, Y. C., & Holzbaur, E. L. F. (2015) · Journal of Cell Science · doi:10.1242/jcs.161216 · Cited by 117
“Using live-cell imaging in cultured neurons, recent studies have found that autophagosomes that undergo axonal transport engulf both mutant SOD1 (Maday et al., 2012) and polyQ-htt (Wong and Holzbaur, 2014a), further demonstrating that autophagy contributes to protein turnover in the axon.”
BackgroundInfluentialSelf-citationMitochondrial quality control: Easy come, easy go
Stotland, A. B., & Gottlieb, R. A. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.12.041 · Cited by 123
“This finding is consistentwith previouswork suggesting that autophagosomes initiate distally in neurons (near the oldest mitochondria) and then migrate towards the soma, where they fuse with lysosomes [135].”
BackgroundRegulation and Roles of Autophagy at Synapses
Nikoletopoulou, V., & Tavernarakis, N. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.03.006 · Cited by 116
Autophagy is essential for oligodendrocyte differentiation, survival, and proper myelination
Bankston, A. N., Forston, M. D., Howard, R. M., Andres, K. R., Smith, A. E., Ohri, S. S., Bates, M. L., Bunge, M. B., & Whittemore, S. R. (2019) · Glia · doi:10.1002/glia.23646 · Cited by 112
Neuronal autophagy and intercellular regulation of homeostasis in the brain
Kulkarni, A., Chen, J., & Maday, S. (2018) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2018.02.008 · Cited by 125
“As autophagosomes travel from the distal axon to the soma, they mature into degradative autolysosomes (Figure 1b) [24,26].”
InfluentialSelf-citationPace, R. D., Skirzewski, M., Daμμe, M., Mattera, R., Mercurio, J. C., Foster, A. M., Cuitiño, L., Jarník, M., Hoffmann, V. J., Morris, H. D., et al. (2018) · PLoS Genetics · doi:10.1371/journal.pgen.1007363 · Cited by 125
Harnessing the Power of the Endosome to Regulate Neural Development
Yap, C. C., & Winckler, B. (2012) · Neuron · doi:10.1016/j.neuron.2012.04.015 · Cited by 121
The involvement of stress granules in aging and aging‐associated diseases
Cao, X., Jin, X., & Liu, B. (2020) · Aging Cell · doi:10.1111/acel.13136 · Cited by 118
Axonal transport and maturation of lysosomes
Ferguson, S. M. (2018) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2018.02.020 · Cited by 111
Mechanisms of neurotrophin trafficking via Trk receptors
Scott-Solomon, E., & Kuruvilla, R. (2018) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2018.03.013 · Cited by 113
“Conversely, one argument against autophagosomes as being the retrograde carriers of the Trk signal is that they are derived from axonal Endoplasmic Reticulum (ER) domains, and not from the plasma membrane at least under basal conditions (Maday et al., 2012).”
BackgroundKymoAnalyzer : a software tool for the quantitative analysis of intracellular transport in neurons
Neumann, S., Chassefeyre, R., Campbell, G. E., & Encalada, S. E. (2016) · Traffic · doi:10.1111/tra.12456 · Cited by 112
“Finally, the analysis of a previously published movie imaging the movement of a monomeric NeonGreen tagged Kinesin Heavy Chain-1 (KHC (1-560)-mNeGr) recombinant protein, showed that KymoAnalyzer can easily be applied for the characterization of in vitro transport (Figure 9F).”
MethodSpreading of tau pathology in A lzheimer's disease by cell‐to‐cell transmission
Mohamed, N., Herrou, T., Plouffe, V., Piperno, N., & Leclerc, N. M. (2013) · European Journal of Neuroscience · doi:10.1111/ejn.12229 · Cited by 116
“distal portion of the axon as well as endosomes (Maday et al., 2012).”
BackgroundAutophagy in neurodegenerative diseases: From pathogenic dysfunction to therapeutic modulation
Martínez‐Vicente, M. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.03.005 · Cited by 114
Dragich, J. M., Kuwajima, T., Hirose‐Ikeda, M., Yoon, M. S., Eenjes, E., Bosco, J. R., Fox, L. M., Lystad, A. H., Oo, T. F., Yarygina, O., et al. (2016) · eLife · doi:10.7554/elife.14810 · Cited by 110
Deneubourg, C., Ramm, M., Smith, L. J., Baron, O., Singh, K., Byrne, S., Duchen, M. R., Gautel, M., Eskelinen, E., Fanto, M., et al. (2021) · Autophagy · doi:10.1080/15548627.2021.1943177 · Cited by 115
“Autophagosomes in particular constitutively form in the distal end of axons and are transported retrogradely to the cell soma for degradation [144,145], and any defect disturbing this essential mechanism is likely to result in neuronal pathology.”
BackgroundGoldsmith, J., Ordureau, A., Harper, J. W., & Holzbaur, E. L. F. (2022) · Neuron · doi:10.1016/j.neuron.2021.12.029 · Cited by 112
Self-citationSequential dynein effectors regulate axonal autophagosome motility in a maturation-dependent pathway
Cason, S. E., Carman, P. J., Duyne, C. V., Goldsmith, J., Domínguez, R., & Holzbaur, E. L. F. (2021) · The Journal of Cell Biology · doi:10.1083/jcb.202010179 · Cited by 108
Self-citationThe Endolysosomal System and Proteostasis: From Development to Degeneration
Winckler, B., Faúndez, V., Maday, S., Cai, Q., Almeida, C. G., & Zhang, H. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.1665-18.2018 · Cited by 111
Self-citationFerguson, S. M. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.04.005 · Cited by 107
Guedes-Dias, P., de Proença, J., Soares, T. R., Leitão-Rocha, A., Pinho, B. R., Duchen, M. R., & Oliveira, J. M. A. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.08.012 · Cited by 107
“The function of acetylcortactin in neurons is mostly unknown [35]; however, given that cortactin is scarce throughout the axons [36,37] – where most autophagosome-fusion events occur [38,39] – cortactinmay not be critical for such events in neurons.”
BackgroundNeisch, A. L., Neufeld, T. P., & Hays, T. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201606082 · Cited by 87
“The distribution differences we see in these in situ experiments are similar to those reported for cultured dorsal root ganglion neurons (Maday et al., 2012).”
BackgroundResultQuality Control in Neurons: Mitophagy and Other Selective Autophagy Mechanisms
Evans, C. S., & Holzbaur, E. L. F. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.06.031 · Cited by 109
“Some of this clearance is nonselective, as aggregates of either mutant superoxide dismutase (SOD) 1 or mutant Htt are readily engulfed by axonal autophagosomes [13, 17].”
BackgroundInfluentialSelf-citationKallergi, E., Daskalaki, A.-D., Kolaxi, A., Camus, C., Ioannou, E., Mercaldo, V., Haberkant, P., Stein, F., Sidiropoulou, K., Dalezios, Y., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28301-z · Cited by 113
Presynaptic autophagy is coupled to the synaptic vesicle cycle via ATG-9
Yang, S., Park, D., Manning, L., Kargbo-Hill, S. E., Cao, M., Zhao, X., Gonzalez, I. J., Dong, Y., Clark, B., Shao, L., et al. (2022) · Neuron · doi:10.1016/j.neuron.2021.12.031 · Cited by 103
“…biogenesis occurs near synapses, and autophagosome biogenesis is coupled to the neuronal activity state (Bunge, 1973; Soukup et al., 2016; Maday et al., 2012; Stavoe et al., 2016; Katsumata et al., 2010; Shehata et al., 2012; Hill et al., 2019; Soykan et al., 2021; Wang et al., 2015;…”
Eaten alive: novel insights into autophagy from multicellular model systems
Zhang, H., & Baehrecke, E. H. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.03.001 · Cited by 102
Autophagy in neuronal cells: general principles and physiological and pathological functions
Daμμe, M., Suntio, T., Säftig, P., & Eskelinen, E. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1361-4 · Cited by 109
“In primary neurons, autophagosomes constitutively form in the tips of neurites and then travel towards the cell soma, undergoing fusion with endosomal and lysosomal vesicles and turning acidic during the transport [66, 138] (Fig.”
Bustamante, H. A., González, A., Cerda‐Troncoso, C., Shaughnessy, R., Carola Otth, L., Soza, A., & Burgos, P. V. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00126 · Cited by 102
“Studies show that in neurons autophagosome biogenesis begins in distal axons and its maturation process occurs along the axon toward the cell body through amechanism that depends on retrograde transport (Maday et al., 2012).”
BackgroundAutophagy core machinery: overcoming spatial barriers in neurons
Ariosa, A., & Klionsky, D. J. (2016) · Journal of Molecular Medicine · doi:10.1007/s00109-016-1461-9 · Cited by 108
Protein Homeostasis in Amyotrophic Lateral Sclerosis: Therapeutic Opportunities?
Webster, C. P., Smith, E. F., Shaw, P. J., & Vos, K. J. D. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00123 · Cited by 109
“Autophagosome transport in neurons is regulated by the dynein–dynactin complex and therefore disruption of this complex may lead to aberrant autophagosome transport and protein aggregation (Ravikumar et al., 2005; Maday et al., 2012; Maday and Holzbaur, 2014).”
BackgroundDefective Axonal Transport of Rab7 GTPase Results in Dysregulated Trophic Signaling
Zhang, K., Kenan, R. F. B., Osakada, Y., Xu, W. L., Sinit, R. S., Chen, L., Zhao, X., Chen, J.-Y., Cui, B., & Wu, C. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.4322-12.2013 · Cited by 99
“Consistent with this notion, the autophagosomes are initiated at the distal terminals and become mature during transport toward the cell body in DRG neurons (Maday et al., 2012).”
BackgroundDCTN1-related neurodegeneration: Perry syndrome and beyond
Konno, T., Ross, O. A., Teive, H. A. G., Sławek, J. W., Dickson, D. W., & Wszołek, Z. K. (2017) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2017.06.004 · Cited by 98
Hou, K., Xu, D., Li, F., Chen, S., & Li, Y. (2019) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2019.03.015 · Cited by 99
Mitophagy regulates integrity of mitochondria at synapses and is critical for synaptic maintenance
Han, S., Jeong, Y. Y., Sheshadri, P., Su, X. Y., & Cai, Q. (2020) · EMBO Reports · doi:10.15252/embr.201949801 · Cited by 96
“It has been established that autophagosomes are robustly generated in distal axons and move in a retrograde direction for lysosomal clearance in the soma (Maday et al , 2012; Cheng et al , 2015a,b; Maday & Holzbaur, 2016).”
Autophagy Negatively Regulates Early Axon Growth in Cortical Neurons
Ban, B.-K., Jun, M.-H., Ryu, H.-H., Jang, D., Ahmad, S. T., & Lee, J. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00627-13 · Cited by 101
The impact of cytoskeletal organization on the local regulation of neuronal transport
Nirschl, J., Ghiretti, A. E., & Holzbaur, E. L. F. (2017) · Nature reviews. Neuroscience · doi:10.1038/nrn.2017.100 · Cited by 102
Self-citationGlycan sulfation patterns define autophagy flux at axon tip via PTPRσ-cortactin axis
Sakamoto, K., Ozaki, T., Ko, Y., Tsai, C.-F., Gong, Y., Morozumi, M., Ishikawa, Y., Uchimura, K., Nadanaka, S., Kitagawa, H., et al. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0274-x · Cited by 95
Castle, M. J., Perlson, E., Holzbaur, E. L. F., & Wolfe, J. H. N. (2013) · Molecular Therapy · doi:10.1038/mt.2013.237 · Cited by 98
“Total Distance Progressed (μm) 83 (97) 48 (56) 36 (32) 36 (38) k.”
Self-citationDe Pace, R., Ghosh, S., Ryan, V. H., Sohn, M., Jarnik, M., Rezvan Sangsari, P., Morgan, N. Y., Dale, R. K., Ward, M. E., & Bonifacino, J. S. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01619-1 · Cited by 81
“The population of retrograde lysosome-related vesicles includes mature lysosomes, late endosomes, autolysosomes (fusion of lysosomes with autophagosomes) and/or amphisomes (fusion of lysosomes with late endosomes) 15–18 .”
Autophagy, Cellular Aging and Age-related Human Diseases
Cheon, S. Y., Kim, H. J., Rubinsztein, D. C., & Lee, J. E. (2019) · Experimental Neurobiology · doi:10.5607/en.2019.28.6.643 · Cited by 95
“The minus-end-directed dynein and plus-end-directed kinesin are key motor proteins that transport autophagosomes [28-30].”
BackgroundSomatic autophagy of axonal mitochondria in ischemic neurons
Zheng, Y., Zhang, X., Wu, X., Jiang, L., Ahsan, A., Ma, S., Xiao, Z., Han, F., Qin, Z., Hu, W., et al. (2019) · The Journal of Cell Biology · doi:10.1083/jcb.201804101 · Cited by 94
“In contrast, autophagosomes and lysosomes were more concentrated in soma (Sagné et al., 2001; Maday et al., 2012; Faŕıas et al., 2017), raising a question as to how neuronal mitophagy is spatially regulated (Ashrafi et al.”
The synaptic maintenance problem: membrane recycling, Ca2+ homeostasis and late onset degeneration
Борисович, Б. И., & Hiesinger, P. R. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-23 · Cited by 89
“In another recent study, autophagosome biogenesis was shown at the neurite tip of neurons of the basal root ganglia [51].”
BackgroundEnhancing autophagy in Alzheimer's disease through drug repositioning
Eshraghi, M., Ahmadi, M., Afshar, S., Lorzadeh, S., Adlimoghaddam, A., Rezvani Jalal, N., West, R., Dastghaib, S., Igder, S., Torshizi, S. R. N., et al. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108171 · Cited by 89
Roles for neuronal and glial autophagy in synaptic pruning during development
Lieberman, O. J., McGuirt, A. F., Tang, G., & Sulzer, D. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.04.017 · Cited by 87
“In neurons, autophagosome formation has primarily been studied in the distal axon and soma (Hollenbeck, 1993; Maday and Holzbaur, 2016, 2014; Maday et al., 2012).”
BackgroundAndres‐Alonso, M., Ammar, M. R., Butnaru, I., Gomes, G. M., Sanhueza, G. A., Raman, R., Yuanxiang, P., Borgmeyer, M., Lopez‐Rojas, J., Raza, S. A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13224-z · Cited by 84
Lie, P. P. Y., Yang, D.-S., Stavrides, P., Goulbourne, C. N., Zheng, P., Mohan, P. S., Cataldo, A. M., & Nixon, R. A. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109034 · Cited by 97
“In neurons, axonal endosomes and autophagosomes acquire Rab7 and LAMP1 while maturing into LEs and amphisomes, which then undergo progressive acidification and further maturation toward lysosomal identity during their retrograde transport (Cheng et al., 2015; Deinhardt et al., 2006; Kuijpers et al., 2020; Lee et al.,…”
BackgroundResultExpression of WIPI2B counteracts age-related decline in autophagosome biogenesis in neurons
Stavoe, A. K., Gopal, P. P., Gubas, A., Tooze, S. A., & Holzbaur, E. L. (2019) · eLife · doi:10.7554/elife.44219 · Cited by 82
“other systems by cellular stressors, there is little evidence that neuronal autophagy is substantially upregulated by either proteomic stress (Maday et al., 2012; Wong and Holzbaur, 2014) or nutrient deprivation (Maday and Holzbaur, 2016).”
BackgroundMethodInfluentialSelf-citationPromoting Autophagic Clearance: Viable Therapeutic Targets in Alzheimer's Disease
Friedman, L. G., Qureshi, Y. H., & Yu, W. H. (2014) · Neurotherapeutics · doi:10.1007/s13311-014-0320-z · Cited by 89
Neuronal endolysosomal transport and lysosomal functionality in maintaining axonostasis
Roney, J. C., Cheng, X., & Sheng, Z. (2022) · The Journal of Cell Biology · doi:10.1083/jcb.202111077 · Cited by 91
Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis
Jiang, M., Esteve-Rudd, J., Lopes, V. S., Diemer, T., Lillo, C., Rump, A., & Williams, D. S. (2015) · Journal of Cell Biology · doi:10.1083/jcb.201410112 · Cited by 85
Impulse Conduction Increases Mitochondrial Transport in Adult Mammalian Peripheral Nerves In Vivo
Sajic, M., Mastrolia, V., Lee, C. Y., Trigo, D., Sadeghian, M., Mosley, A. J., Gregson, N. A., Duchen, M. R., & Smith, K. J. (2013) · PLoS Biology · doi:10.1371/journal.pbio.1001754 · Cited by 85
“Previous studies suggested that mitochondrial degradation and autophagy is indeed initiated at the axonal terminal of cultured DRG neurons, and that the autophagosomes are then transported retrogradely towards the cell body, becoming increasingly acidified along the way [19].”
BackgroundSung, H., Tandarich, L. C., Nguyen, K. K., & Hollenbeck, P. J. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.0633-16.2016 · Cited by 85
“Parkin-dependent mitophagy is undetectable in motor neurons in vivo Studies in embryonic neurons in vitro have shown that autophagosomes initiate distally and undergo maturation during their retrograde transport (Maday et al., 2012; Maday and Holzbaur, 2014).”
BackgroundResultInfluentialIvankovic, D., Drew, J., Lesept, F., White, I. J., López‐Doménech, G., Tooze, S. A., & Kittler, J. T. (2019) · Autophagy · doi:10.1080/15548627.2019.1615302 · Cited by 89
Kendrick, A. A., Dickey, A. M., Redwine, W. B., Tran, P. T., Vaites, L. P., Dzieciątkowska, M., Harper, J. W., & Reck‐Peterson, S. L. (2019) · The Journal of Cell Biology · doi:10.1083/jcb.201812170 · Cited by 81
“, 2010), autophagosomes (Maday et al., 2012), and protein aggregates (Kamal et al.”
BackgroundLysosome motility and distribution: Relevance in health and disease
Oyarzún, J. E., Lagos, J., Vázquez, M. C., Valls, C., de la Fuente, C., Yuseff, M.-I., Alvarez, A. R., & Zanlungo, S. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2019.03.009 · Cited by 88
Lee, J., Rao, M. V., Yang, D., Stavrides, P. H., Im, E., Pensalfini, A., Huo, C., Sarkar, P., Yoshimori, T., & Nixon, R. A. (2018) · Autophagy · doi:10.1080/15548627.2018.1528812 · Cited by 82
Origin of the Autophagosome Membrane in Mammals
Wei, Y., Liu, M., Li, X., Liu, J., & Li, H. (2018) · BioMed Research International · doi:10.1155/2018/1012789 · Cited by 87
Microtubule-directed transport of purine metabolons drives their cytosolic transit to mitochondria
Chan, C. Y., Pedley, A. M., Kim, D., Xia, C., Zhuang, X., & Benkovic, S. J. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1814042115 · Cited by 84
Sex Differences in Autophagy Contribute to Female Vulnerability in Alzheimer's Disease
Congdon, E. E. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00372 · Cited by 80
“In isolated neurons the majority of autophagosome formation occurs in the distal axon, with the vesicles undergoing maturation as they are transported to the soma (Maday et al., 2012; Maday and Holzbaur, 2014).”
BackgroundWhite, J. A., Anderson, E., Zimmerman, K., Zheng, K. H., Rouhani, R., & Gunawardena, S. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv415 · Cited by 67
“Work has also shown that Rab7 and LC3 (a marker for autophagosomes) are together during the transport of autophagosomes at growth cones (57) and that the retrograde movement of autophagosomes is required for their maturation (58).”
BackgroundAn update on the interactions between Alzheimer's disease, autophagy and inflammation
Bostancıklıoğlu, M. (2019) · Gene · doi:10.1016/j.gene.2019.04.040 · Cited by 78
Devireddy, S., Liu, A., Lampe, T., & Hollenbeck, P. J. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.1198-15.2015 · Cited by 78
“Despite clear evidence of axonal mitochondrial turnover in embryonic neurons in culture (Maday et al., 2012), it remains likely that much of the mitochondrial processing in the intact nervous system actually occurs in the somatic compartment (Cai et al., 2012).”
BackgroundCytoplasmic sphingosine-1-phosphate pathway modulates neuronal autophagy
Moruno-Manchon, J. F., Uzor, N.-E., Dabaghian, Y. A., Furr-Stimming, E. E., Finkbeiner, S. M., & Tsvetkov, A. S. (2015) · Scientific Reports · doi:10.1038/srep15213 · Cited by 77
Uemura, N., Koike, M., Ansai, S., Kinoshita, M., Ishikawa‐Fujiwara, T., Matsui, H., Naruse, K., Sakamoto, N., Uchiyama, Y., Todo, T., et al. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005065 · Cited by 82
“A previous study reported that autophagosomes are formed in the distal part of the axon and undergo retrograde transport toward the cell body[48].”
BackgroundLüningschrör, P., Binotti, B., Dombert, B., Heimann, P., Pérez-Lara, Á., Slotta, C., Thau‐Habermann, N., von Collenberg, C. R., Karl, F., Daμμe, M., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00689-z · Cited by 79
Exploring new pathways of neurodegeneration in ALS: The role of mitochondria quality control
Palomo, G. M., & Manfredi, G. (2014) · Brain Research · doi:10.1016/j.brainres.2014.09.065 · Cited by 81
Kinesin’s Neck-Linker Determines its Ability to Navigate Obstacles on the Microtubule Surface
Hoeprich, G. J., Thompson, A. R., McVicker, D. P., Hancock, W. O., & Berger, C. L. (2014) · Biophysical Journal · doi:10.1016/j.bpj.2014.02.034 · Cited by 80
Amadoro, G., Corsetti, V., Florenzano, F., Atlante, A., Bobba, A., Nicolin, V., Nori, S. L., & Calissano, P. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00018 · Cited by 77
“Daniel Ortuño-Sahagun, Centro Universitario de Ciencias Biológicas y Agropecuarias, Mexico Nibaldo C. Inestrosa, Pontifical Catholic University of Chile, Chile Alberto Lazarowski, University of Buenos Aires, Argentina *Correspondence: Giuseppina Amadoro, Institute of Translational Pharmacology – National Research Coun…”
BackgroundInfluentialThe Journey of the Synaptic Autophagosome: A Cell Biological Perspective
Kargbo-Hill, S. E., & Colón-Ramos, D. A. (2020) · Neuron · doi:10.1016/j.neuron.2020.01.018 · Cited by 72
“…and lysosomal markers have been proposed as biomarkers for disease detection (Mputhia et al., 2019), and a growing number of pharmacological agents seek to modulate the autophagy pathway as a therapeutic intervention for neurodegenerative diseases associated with autophagy (Malik et al., 2019).”
BackgroundInfluentialKargbo-Hill, S. E., Kauffman, K. J., Krout, M., Richmond, J. E., Melia, T. J., & Colón‐Ramos, D. A. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.02.013 · Cited by 70
“, 2016)) begin progressive maturation (Maday et al., 2012; Neisch et al., 2017; Vanhauwaert et al., 2017), and once in the cell body, they are targeted for degradation and clearance through mechanisms that are not well understood.”
BackgroundInfluentialDifferential regulation of autophagy during metabolic stress in astrocytes and neurons
Kulkarni, A., Dong, A., Kulkarni, V. V., Chen, J., Laxton, O., Anand, A., & Maday, S. (2019) · Autophagy · doi:10.1080/15548627.2019.1703354 · Cited by 81
“We previously established a vectorial pathway for autophagy in the axon that delivers cargo from the distal axon to the soma for degradation in neurons [32,33].”
BackgroundSelf-citationCompartment‐specific dynamics and functions of autophagy in neurons
Kulkarni, V. V., & Maday, S. (2017) · Developmental Neurobiology · doi:10.1002/dneu.22562 · Cited by 77
“2B) (Hollenbeck, 1993; Maday et al., 2012; Maday and Holzbaur, 2014; Lee et al., 2011; Yue, 2007).”
InfluentialSelf-citationThe metazoan protein disaggregase and amyloid depolymerase system
Torrente, M. P., & Shorter, J. (2013) · Prion · doi:10.4161/pri.27531 · Cited by 75
Ghiretti, A. E., Thies, E., Tokito, M. K., Lin, T., Ostap, E. M., Kneussel, M., & Holzbaur, E. L. F. (2016) · Neuron · doi:10.1016/j.neuron.2016.10.003 · Cited by 72
“Simultaneously, cargoes from distal axonal and dendritic regions undergo sustained transport back to the soma (Cohen et al., 2011; Maday et al., 2012).”
Self-citationAutophagy and proteostasis in the control of synapse aging and disease
Liang, Y., & Sigrist, S. J. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.12.006 · Cited by 74
Impaired protein degradation in FTLD and related disorders
Götzl, J. K., Lang, C. M., Haass, C., & Capell, A. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.04.008 · Cited by 75
Light-Activated ROS Production Induces Synaptic Autophagy
Hoffmann, S., Orlando, M., Andrzejak, E., Bruns, C., Trimbuch, T., Rosenmund, C., Garner, C. C., & Ackermann, F. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.1317-18.2019 · Cited by 71
“…several studies have demonstrated that autophagosomes form in axons upon starvation, rapamycin treatment as well as enhanced synaptic activity (Maday and Holzbaur, 2014; Wang et al., 2015) and become retrogradely transported along the axon toward the soma (Maday et al., 2012; Cheng et al., 2015a).”
BackgroundTubulin polyglutamylation is a general traffic-control mechanism in hippocampal neurons
Bodakuntla, S., Schnitzler, A., Villablanca, C., González-Billault, C. E., Bièche, I., Janke, C., & Magiera, M. M. (2020) · Journal of Cell Science · doi:10.1242/jcs.241802 · Cited by 73
“S3) to label lysosomes but also autophagosomes (Maday et al., 2012), and expression of the lysosome-associated membrane protein 1 (LAMP1)-GFP (Fig.”
BackgroundAutophagosome maturation and lysosomal fusion
Ganley, I. G. (2013) · Essays in Biochemistry · doi:10.1042/bse0550065 · Cited by 79
“Perhaps the most striking evidence for this has come from studies in primary neurons that shows autophagosomes form distally, but migrate inwards along the axon in a microtubule- and dynein-dependent manner until fusion with endosomes and lysosomes [16].”
Neuronal Autophagy in Synaptic Functions and Psychiatric Disorders
Tomoda, T., Yang, K., & Sawa, A. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.07.018 · Cited by 72
“Recent cellular imaging studies revealed that the autophagosomes are not only constitutively generated in axons (17,18), but are also increased in number upon synaptic activity, either through increased local biogenesis or recruitment of pre-existing autophagosomes to the site of synaptic activation (42–45).”
BackgroundAber, E. R., Griffey, C. J., Davies, T., Li, A. M., Yang, Y. J., Croce, K. R., Goldman, J. E., Grutzendler, J., Canman, J. C., & Yamamoto, A. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111480 · Cited by 73
A cryo-ET survey of microtubules and intracellular compartments in mammalian axons
Foster, H. E., Ventura Santos, C., & Carter, A. P. (2022) · Journal of Cell Biology · doi:10.1083/jcb.202103154 · Cited by 69
“The return of components to the cell body depends on cytoplasmic dynein-1, which is responsible for transporting endocytic vesicles, autophagosomes, and lysosomes (Gowrishankar et al., 2017; Maday et al., 2012; Wang et al., 2016).”
BackgroundRegulation of neuronal autophagy and the implications in neurodegenerative diseases
Cai, Q., & Ganesan, D. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105582 · Cited by 70
Autophagy-mediated Regulation of BACE1 Protein Trafficking and Degradation
Feng, T., Tammineni, P., Agrawal, C., Jeong, Y. Y., & Cai, Q. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.766584 · Cited by 69
“Autophagosomes are predominantly generated in distal axons and then undergo predominant retrograde transport toward the soma (23, 29, 30, 32, 33).”
BackgroundAxonal autophagy: Mini-review for autophagy in the CNS
Stavoe, A. K., & Holzbaur, E. L. F. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.03.025 · Cited by 72
“Still to be determined is the nature of the molecular timer that leads to the steady production of new autophagosomes, at a rate of ~7–20 events/hr [28, 30] in mammalian neurons in vitro and ~2 events/hr in vivo in C.”
BackgroundInfluentialSelf-citationMechanism and Regulation of Autophagy and Its Role in Neuronal Diseases
Hu, Z., Yang, B., Mo, X., & Xiao, H. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-8921-4 · Cited by 69
Ji, C., Zhao, H., Chen, D., Zhang, H., & Zhao, Y. G. (2021) · Current Biology · doi:10.1016/j.cub.2021.01.081 · Cited by 66
Subcellular proteomics of dopamine neurons in the mouse brain
Hobson, B. D., Choi, S. J., Mosharov, E. V., Soni, R. K., Sulzer, D., & Sims, P. A. (2022) · eLife · doi:10.7554/elife.70921 · Cited by 68
“Many autophagosomes formed in distal axons are transported back to the soma prior to fusion with lysosomes (Maday et al., 2012), although other findings implicate local autophagic degradation of damaged mitochondria in axons (Ashrafi et al., 2014).”
Mitochondria dynamism: of shape, transport and cell migration
da Silva, A. F., Mariotti, F. R., Máximo, V., & Campello, S. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1557-8 · Cited by 75
“Subsequently, an uneven fission event produces a large stationary mitochondria and a smaller one that is targeted for degradation [65, 66].”
BackgroundStress-Induced CDK5 Activation Disrupts Axonal Transport via Lis1/Ndel1/Dynein
Klinman, E., & Holzbaur, E. L. F. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.06.032 · Cited by 66
“We also examined the effects of the Ndel1 mutant on autophagosome transport, as the pronounced retrograde motion of these organelles is dynein mediated (Maday et al., 2012).”
BackgroundMethodInfluentialSelf-citationYe, X., Feng, T., Tammineni, P., Chang, Q., Jeong, Y. Y., Margolis, D. J., Cai, H., Kusnecov, A. W., & Cai, Q. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.2851-16.2017 · Cited by 62
“Given the fact that (1) autophagosomes are predominantly generated in distal axons (Maday et al., 2012) and (2) retrograde transport of autophagosomes toward the soma is driven by LE-loaded dynein–Snapin complexes upon fusion of autophagosomes with LEs (Cheng et al., 2015), Snapinenhanced…”
BackgroundAutophagy-Mediated Cholesterol Trafficking Controls Steroid Production
Texada, M. J., Malita, A., Christensen, C., Dall, K. B., Færgeman, N. J., Nagy, S., Halberg, K. A., & Rewitz, K. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.01.007 · Cited by 63
Lieberman, O. J., & Sulzer, D. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.12.028 · Cited by 66
Live Observation of Two Parallel Membrane Degradation Pathways at Axon Terminals
Jin, E. J., Kiral, F. R., Özel, M. N., Burchardt, L. S., Osterland, M., Epstein, D. J., Wolfenberg, H., Prohaska, S., & Hiesinger, P. R. (2018) · Current Biology · doi:10.1016/j.cub.2018.02.032 · Cited by 65
“In the case of (macro-) autophagy, the formation of autophagosomes occurs at axon terminals [10, 26, 27], whereas degradation is thought to occur during and after retrograde transport back to the cell body [8, 9, 27].”
A Presynaptic Perspective on Transport and Assembly Mechanisms for Synapse Formation
Rizalar, F. S., Roosen, D. A., & Haucke, V. (2020) · Neuron · doi:10.1016/j.neuron.2020.09.038 · Cited by 67
Roney, J. C., Li, S., Farfel‐Becker, T., Huang, N., Sun, T., Xie, Y., Cheng, X., Lin, M.-Y., Platt, F. M., & Sheng, Z. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.03.032 · Cited by 71
Alzheimer's Disease-Related Misfolded Proteins and Dysfunctional Organelles on Autophagy Menu
Correia, S. C., Resende, R., Moreira, P. I., & Pereira, C. (2015) · DNA and Cell Biology · doi:10.1089/dna.2014.2757 · Cited by 66
“Autophagosomes carrying the cellular cargoes are transported along the microtubule tracks toward the soma (which contains the highest concentration of lysosomes), where they fuse with lysosomes to form the au-tophagolysosome (Maday and Holzbaur, 2012a; Maday et al. , 2012b).”
MitoTimer: a novel protein for monitoring mitochondrial turnover in the heart
Gottlieb, R. A., & Stotland, A. B. (2014) · Journal of Molecular Medicine · doi:10.1007/s00109-014-1230-6 · Cited by 66
“Interestingly, it has been reported that autophagosomes initiate distally in neurons (near the oldest mitochondria) and then migrate towards the soma, where they fuse with lysosomes [41].”
BackgroundGigaxonin E3 ligase governs ATG16L1 turnover to control autophagosome production
Scrivo, A., Codogno, P., & Bomont, P. (2019) · Nature Communications · doi:10.1038/s41467-019-08331-w · Cited by 64
Metadata
- Authors
- Maday, S., Wallace, K. E., & Holzbaur, E. L. F.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Maday, Sandra
- Holzbaur, Erika L.F.
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2012-02-13
- Volume
- 196
- Issue
- 4
- Pages
- 407-417
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC3283992
- OpenAlex
- W2137686667
- Cited by
- 681
- References
- 30
- Citations by year
- 2026: 34 · 2025: 45 · 2024: 56 · 2023: 37 · 2022: 66 · 2021: 65 · 2020: 52 · 2019: 55 · 2018: 53 · 2017: 39 · 2016: 47 · 2015: 52 · 2014: 38 · 2013: 27 · 2012: 13
- FWCI
- 31.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R37NS060698, NS060698, R01NS060698)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- autophagosomes, autophagy, dorsal root ganglion neurons, axonal transport, dynein, kinesin, retrograde transport, autophagosome maturation, autolysosomes, lysosomes, mitochondria, ubiquitin, neurodegeneration
- MeSH terms
- Superoxide Dismutase-1, Animals, Autophagy, Axons, Biological Transport, Cell Compartmentation, Dyneins, Fluorescent Antibody Technique, Image Processing, Computer-Assisted, Mice, Transgenic, Neurons, Phagosomes, Superoxide Dismutase, Green Fluorescent Proteins, Mice
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