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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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“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
Cited by
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Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,897
Self-citationThe pathways of mitophagy for quality control and clearance of mitochondria
Ashrafi, G., & Schwarz, T. L. (2013) · Cell Death & Differentiation · doi:10.1038/cdd.2012.81 · Cited by 1,900
“In addition, distal formation and retrograde transport of autophagosomes in axons of primary neurons have been reported and mitochondrial markers have been observed in these autophagosomes.(110) Nevertheless, it is not certain that retrograde transport of an autophagosome to the soma is strictly required as lysosomal…”
BackgroundWong, Y. C., & Holzbaur, E. L. F. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1405752111 · Cited by 812
“This process of LC3 puncta to ring formation lasted ∼5 min, similar to the kinetics of basal autophagy observed in primary neurons (37).”
ResultSelf-citationAxonal transport deficits and neurodegenerative diseases
Millecamps, S., & Julien, J.-P. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3380 · Cited by 755
Mammalian Autophagy: How Does It Work?
Bento, C. F., Renna, M., Ghislat, G., Puri, C., Ashkenazi, A., Vicinanza, M., Menzies, F. M., & Rubinsztein, D. C. (2016) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014556 · Cited by 711
Axonal transport: cargo-specific mechanisms of motility and regulation
Maday, S., Twelvetrees, A. E., Moughamian, A. J., & Holzbaur, E. L. F. (2014) · Neuron · doi:10.1016/j.neuron.2014.10.019 · Cited by 683
“Dynein is a much weaker motor than kinesin-1 or kinesin-2; there is general although not complete consensus that the stall force formammalian cytoplasmic dynein is 1 pN (Mallik et al., 2004; Schroeder et al., 2010).”
BackgroundSelf-citationThe cytoplasmic dynein transport machinery and its many cargoes
Reck‐Peterson, S. L., Redwine, W. B., Vale, R. D., & Carter, A. P. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0004-3 · Cited by 680
“In neurons, autophagosomes can form at the axon tip 100 and then fuse with lysosome-associated membrane glycoprotein 1 (LAMP1)-marked or RAB7-marked late endosomes to initiate transport towards the cell body 100–102 .”
Machinery, regulation and pathophysiological implications of autophagosome maturation
Zhao, Y. G., Codogno, P., & Zhang, H. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00392-4 · Cited by 582
Mitostasis in Neurons: Maintaining Mitochondria in an Extended Cellular Architecture
Misgeld, T., & Schwarz, T. L. (2017) · Neuron · doi:10.1016/j.neuron.2017.09.055 · Cited by 562
Functions and mechanics of dynein motor proteins
Roberts, A. J., Kon, T., Knight, P. J., Sutoh, K., & Burgess, S. A. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3667 · Cited by 565
Ashrafi, G., Schlehe, J. S., LaVoie, M. J., & Schwarz, T. L. (2014) · Journal of Cell Biology · doi:10.1083/jcb.201401070 · Cited by 502
“S2, B and C) as previously observed (Maday et al., 2012).”
BackgroundResultInfluentialDefects in trafficking bridge Parkinson’s disease pathology and genetics
Abeliovich, A., & Gitler, A. D. (2016) · Nature · doi:10.1038/nature20414 · Cited by 462
Gowrishankar, S., Yuan, P., Wu, Y., Schrag, M., Paradise, S., Grutzendler, J., De Camilli, P., & Ferguson, S. M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1510329112 · Cited by 406
“These initial steps of convergence between the endocytic and autophagic pathways are accompanied by luminal acidification and coincide with a switch toward a predominantly dynein-driven transport in the retrograde direction (48, 52).”
BackgroundInfluentialBidirectional cargo transport: moving beyond tug of war
Hancock, W. O. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3853 · Cited by 447
Maturation of autophagosomes and endosomes: A key role for Rab7
Hyttinen, J. M. T., Niittykoski, M., Salminen, A., & Kaarniranta, K. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.11.018 · Cited by 437
“As will be discussed later, common molecular motors transport endosomes and autophagosomes alongmicrotubules in these maturation processes, including the small Rab GTPase proteins [24], discussed closely in the following chapters.”
BackgroundMitochondrial trafficking and anchoring in neurons: New insight and implications
Sheng, Z. (2014) · The Journal of Cell Biology · doi:10.1083/jcb.201312123 · Cited by 429
“A recent study reports the predominant retrograde transport of autophagosomes including those engulfing damaged mitochondria from distal axons to the soma (Maday et al., 2012).”
Wong, Y., & Holzbaur, E. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1870-13.2014 · Cited by 380
“We used a dual-color mCherry-EGFPLC3 reporter; the GFP moiety is preferentially quenched as the compartment matures and acidifies (Kimura et al., 2007; Pankiv et al., 2007), leading to an increase in red-only autophagosomes more proximal to the soma (Maday et al., 2012).”
BackgroundMethodResultInfluentialSelf-citationMultiple Roles of the Small GTPase Rab7
Guerra, F., & Bucci, C. (2016) · Cells · doi:10.3390/cells5030034 · Cited by 414
“autophagosomes exhibit bidirectional motility in distal regions, but then escape from this distal pool to become fully acidified through fusion with late endosomes and lysosomes in the perinuclear region [143].”
BackgroundInfluentialAutophagosome Biogenesis in Primary Neurons Follows an Ordered and Spatially Regulated Pathway
Maday, S., & Holzbaur, E. L. F. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.06.001 · Cited by 372
“The robust retrograde transport of autophagosomes along the axon was exhibited throughout development (5–16 DIV), with 87% ± 1.9% (±SEM) of axonal autophagosomes moving a net distance of R5 mm in the retrograde direction (Figures 3D and 3E).”
BackgroundMethodResultInfluentialSelf-citationAxonal transport: Driving synaptic function
Guedes-Dias, P., & Holzbaur, E. L. F. (2019) · Science · doi:10.1126/science.aaw9997 · Cited by 355
“Autophagosomes initially showbidirectional oscillatory movement before engaging in processive retrograde transport (154).”
BackgroundSelf-citationMolecular neurobiology of mTOR
Switon, K., Kotulska, K., Janusz, A., Zmorzyńska, J., & Jaworski, J. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.11.017 · Cited by 405
“Autophagosomes are continuously generated at neurite tips and later transported toward the cell body while simultaneously undergoing maturation (Maday et al., 2012; Maday and Holzbaur, 2014).”
Autophagy in Alzheimer’s disease pathogenesis: Therapeutic potential and future perspectives
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Zhao, Y. G., & Zhang, H. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201810099 · Cited by 375
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Martin, D. D. O., Ladha, S., Ehrnhoefer, D. E., & Hayden, M. R. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.09.003 · Cited by 357
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Li, Q., Liu, Y., & Sun, M. (2016) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-016-0386-8 · Cited by 337
“Autophagosomes in neurons majorly formed at axon tip and gradually matured when they are retrograde transporting along axons (Maday et al. 2012).”
BackgroundInfluentialStavoe, A. K. H., & Holzbaur, E. L. F. (2019) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100818-125242 · Cited by 328
“These autophagosomes were then rapidly transported back to the cell body (Cheng et al. 2015, Lee et al. 2011, Maday & Holzbaur 2014, Maday et al. 2012).”
BackgroundInfluentialSelf-citationCompartment-Specific Regulation of Autophagy in Primary Neurons
Maday, S., & Holzbaur, E. L. F. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.4401-15.2016 · Cited by 309
“…originating from distinct neuronal compartments Previous work has identified a robust pathway for autophagosome biogenesis and maturation in axons (Lee et al., 2011; Maday et al., 2012; Maday and Holzbaur, 2014), suggesting that there may be compartment-specific regulation of autophagy in neurons.”
BackgroundResultInfluentialSelf-citationJIP1 regulates the directionality of APP axonal transport by coordinating kinesin and dynein motors
Fu, M., & Holzbaur, E. L. F. (2013) · The Journal of Cell Biology · doi:10.1083/jcb.201302078 · Cited by 277
“However, both in vitro and cellular studies suggest that opposing motors can bind simultaneously to cargos (Soppina et al., 2009; Hendricks et al., 2010; Encalada et al., 2011; Maday et al., 2012).”
Self-citationParkin-mediated mitophagy in mutant hAPP neurons and Alzheimer's disease patient brains
Ye, X., Sun, X., Starovoytov, V., & Cai, Q. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv056 · Cited by 274
“lysosomes enriched in the proximal regions of neurons (53).”
BackgroundCharacterization of LAMP1-labeled nondegradative lysosomal and endocytic compartments in neurons
Cheng, X.-T., Xie, Y.-X., Zhou, B., Huang, N., Farfel-Becker, T., & Sheng, Z.-H. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201711083 · Cited by 294
“Instead, these LAMP1-positive organelles are likely intermediates of endocytic and autophagic pathways and lysosomal biogenesis (Hollenbeck, 1993; Lee et al., 2011; Maday et al., 2012, 2014; Cheng et al., 2015).”
BackgroundLysosome trafficking and signaling in health and neurodegenerative diseases
Lie, P. P. Y., & Nixon, R. A. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.05.015 · Cited by 277
Integrated regulation of motor-driven organelle transport by scaffolding proteins
Fu, M., & Holzbaur, E. L. F. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.05.002 · Cited by 266
Self-citationMicrotubule-Based Transport and the Distribution, Tethering, and Organization of OrganellesPreprint
Barlan, K., & Gelfand, V. I. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a025817 · Cited by 284
“Because these interorganelle interactions do not occur in the distal tip, translocation toward the cell body appears to be required for autophagosome maturation and the ultimate degradation of their contents (Maday et al. 2012).”
BackgroundAxonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes
Cheng, X.-T., Zhou, B., Lin, M.-Y., Cai, Q., & Sheng, Z.-H. (2015) · Journal of Cell Biology · doi:10.1083/jcb.201412046 · Cited by 227
“Dynein is the primary motor driving retrograde transport of both LEs and AVs from distal axons to the soma (Cai et al., 2010; Katsumata et al., 2010; Lee et al., 2011; Maday et al., 2012).”
InfluentialMechanism and Regulation of Cytoplasmic Dynein
Cianfrocco, M. A., DeSantis, M. E., Leschziner, A. E., & Reck‐Peterson, S. L. (2015) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100814-125438 · Cited by 245
“…Moughamian et al. 2013, Moughamian & Holzbaur 2012, Splinter et al. 2012, Zhang et al. 2003), and moving with dynein cargo complexes (Deacon et al. 2003, Egan et al. 2012, Lenz et al. 2006, Maday et al. 2012, Moughamian et al. 2013), where it most likely acts as a processivity factor (see below).”
Uittenbogaard, M. N., & Chiaramello, A. (2014) · Current Pharmaceutical Design · doi:10.2174/1381612820666140305224906 · Cited by 246
“Furthermore, recent studies have revealed the colocalization of lysosomal markers and autophagosomes in the distal axons of dorsal root ganglion neurons, congruent with local mitochondrial clearance [69, 70].”
BackgroundRoot, J. T., Merino, P., Nuckols, A., Johnson, M. A., & Kukar, T. L. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105360 · Cited by 243
Rab GTPases and Membrane Trafficking in Neurodegeneration
Kiral, F. R., Kohrs, F. E., Jin, E. J., & Hiesinger, P. R. (2018) · Current Biology · doi:10.1016/j.cub.2018.02.010 · Cited by 249
“Autophagosomes form and capture their cargos at synaptic terminals independently of the cell body (Figure 1) [60].”
BackgroundAutophagy Induction as a Therapeutic Strategy for Neurodegenerative Diseases
Djajadikerta, A., Keshri, S., Tanasa, M. P., Prestil, R., Ryan, L., & Rubinsztein, D. C. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.12.035 · Cited by 244
Volpicelli‐Daley, L. A., Gamble, K. L., Schultheiss, C. E., Riddle, D. M., West, A. B., & Lee, V. M. ‐. (2014) · Molecular Biology of the Cell · doi:10.1091/mbc.e14-02-0741 · Cited by 233
Song, Q., Meng, B., Xu, H., & Mao, Z. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-020-00196-0 · Cited by 244
Wijdeven, R. H. M., Janssen, H., Nahidiazar, L., Janssen, L., Jalink, K., Berlin, I., & Neefjes, J. (2016) · Nature Communications · doi:10.1038/ncomms11808 · Cited by 246
BORC/kinesin-1 ensemble drives polarized transport of lysosomes into the axon
Farías, G. G., Guardia, C. M., De Pace, R., Britt, D. J., & Bonifacino, J. S. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1616363114 · Cited by 228
“This conclusion is consistent with the notion that fusion of lysosomes with autophagosomes contributes to the dynein-dependent retrograde transport of the resulting autolysosomes, in addition to the degradation of their contents (31, 53).”
BackgroundResultInfluentialKIF1A/UNC-104 Transports ATG-9 to Regulate Neurodevelopment and Autophagy at Synapses
Stavoe, A. K. H., Kargbo-Hill, S. E., Hall, D. H., & Colón-Ramos, D. A. (2016) · Developmental Cell · doi:10.1016/j.devcel.2016.06.012 · Cited by 211
Regulation of mitochondrial transport in neurons
Lin, M.-Y., & Sheng, Z. (2015) · Experimental Cell Research · doi:10.1016/j.yexcr.2015.01.004 · Cited by 232
“Autophagosomes engulfing damaged mitochondria at axonal terminals transport predominantly to the soma for maturation and degradation within acidic lysosomes (Maday et al., 2012).”
BackgroundInfluentialNeuronal Aggregates: Formation, Clearance, and Spreading
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“Notably, autophagosome initiation is a constitutive and spatially restricted process in the distal ends of cultured dorsal root ganglion (DRG) neurons (Maday et al., 2012; Yue et al., 2008).”
BackgroundAlterations in Mitochondrial Quality Control in Alzheimer’s Disease
Cai, Q., & Tammineni, P. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2016.00024 · Cited by 226
“…mitochondria, predominantly undergo retrograde transport from distal axons to the soma, which allows for autophagosome maturation and subsequent degradation within mature lysosomes in the proximal regions and soma of neurons (Maday and Holzbaur, 2014; Maday et al., 2012; Cheng et al., 2015).”
BackgroundMicrotubule-based transport – basic mechanisms, traffic rules and role in neurological pathogenesis
Franker, M. A. M., & Hoogenraad, C. C. (2013) · Journal of Cell Science · doi:10.1242/jcs.115030 · Cited by 216
“, 2006), autophagosomes (Maday et al., 2012), intermediate filaments (Li et al.”
BackgroundER stress and impaired autophagy flux in neuronal degeneration and brain injury
Yin, Y., Sun, G., Li, E., Kiselyov, K. I., & Sun, D. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.08.008 · Cited by 218
Fu, M.-M., Nirschl, J. J., & Holzbaur, E. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.04.015 · Cited by 202
“Autophagosome-enriched fractions were prepared from wild type adult mouse brains following a previously described three-step protocol (Maday et al., 2012; Stromhaug et al., 1998).”
MethodSelf-citationAutophagy and Its Normal and Pathogenic States in the Brain
Yamamoto, A., & Yue, Z. (2014) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071013-014149 · Cited by 204
“For neurons, amphisome formation may be especially valid because APs must travel long distances before degradation can occur (Hollenbeck 1993, Larsen et al. 2002, Maday et al. 2012).”
BackgroundTau phosphorylation affects its axonal transport and degradation
Rodríguez-Martín, T., Cuchillo‐Ibáñez, I., Noble, W. J., Nyenya, F., Anderton, B. H., & Hanger, D. P. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.03.015 · Cited by 211
“Autophagosome dynamics in primary neurons has been described by Maday et al. (2012), who found that autophagosome biogenesis occurs distally in the axon.”
BackgroundAutophagy and ALS: mechanistic insights and therapeutic implications
Chua, J. P., De Calbiac, H., Kabashi, E., & Barmada, S. J. (2022) · Autophagy · doi:10.1080/15548627.2021.1926656 · Cited by 189
“neurites to fuse with somatodendritic lysosomes for cargo degradation, with maturation and acidification of the autophagosomal lumen developing en passant [370,372,374].”
BackgroundThe GTPase Rab26 links synaptic vesicles to the autophagy pathway
Binotti, B., Pavlos, N. J., Riedel, D., Wenzel, D., Vorbrüggen, G., Schalk, A. M., Kühnel, K., Boyken, J., Erck, C., Martens, H., et al. (2015) · eLife · doi:10.7554/elife.05597 · Cited by 199
“During their travel they undergo fusion with acidic compartments and finally with the lysosomes (Lee et al., 2011; Maday et al., 2012).”
BackgroundMitochondrial heterogeneity and homeostasis through the lens of a neuron
Pekkurnaz, G., & Wang, X. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00594-w · Cited by 201
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Court, F. A., & Coleman, M. P. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2012.04.001 · Cited by 201
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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., & Garner, C. C. (2017) · Neuron · doi:10.1016/j.neuron.2017.01.026 · Cited by 197
“Moreover, a number of studies have shown that, while autophagosomes are rather dynamic, they predominantly undergo retrograde transport to the soma (Maday et al., 2012).”
Nirschl, J., Magiera, M. M., Lazarus, J. E., Janke, C., & Holzbaur, E. L. F. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.02.046 · Cited by 187
Self-citationDistinct roles for motor neuron autophagy early and late in the SOD1 G93A mouse model of ALS
Rudnick, N. D., Griffey, C. J., Guarnieri, P., Gerbino, V., Wang, X., Piersaint, J. A., Tapia, J. C., Rich, M. M., & Maniatis, T. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1704294114 · Cited by 189
“It has been demonstrated that autophagosomes can form distally at the synapse and retrogradely transport cargo for degradation (48).”
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Chuang, E., Hori, A. M., Hesketh, C. D., & Shorter, J. (2018) · Journal of Cell Science · doi:10.1242/jcs.189928 · Cited by 188
“3B) (Maday and Holzbaur, 2012, 2014, 2016; Maday et al., 2012).”
Mechanisms Orchestrating Mitochondrial Dynamics for Energy Homeostasis
Yu, S. B., & Pekkurnaz, G. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.07.027 · Cited by 184
“Damaged neuronal mitochondria can be removed by local degradation or shipping of intact or small vesicles containing mitochondrial proteins retrogradely to somatodendritic regions for destruction [64,158,159].”
BackgroundAutophagy and mitophagy in ALS
Evans, C. S., & Holzbaur, E. L. F. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.07.005 · Cited by 185
Self-citationAutophagy induction stabilizes microtubules and promotes axon regeneration after spinal cord injury
He, M., Ding, Y., Chu, C., Tang, J. Y., Xiao, Q., & Luo, Z. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1611282113 · Cited by 179
“Accumulating evidence suggests that MTs play important roles in the regulation of autophagosome formation and transportation in axons (33, 64).”
BackgroundLewis, T. L., Turi, G. F., Kwon, S., Losonczy, A., & Polleux, F. (2016) · Current Biology · doi:10.1016/j.cub.2016.07.064 · Cited by 167
Tammineni, P., Ye, X., Feng, T., Aikal, D., & Cai, Q. (2017) · eLife · doi:10.7554/elife.21776 · Cited by 175
“Microtubulebased long-distance axonal transport is essential for autophagic clearance because autophagosomes are predominantly generated in distal axons and rely heavily on retrograde transport toward the soma for lysosomal proteolysis (Cheng et al., 2015a, 2015b; Lee et al., 2011a; Maday and Holzbaur, 2016; Maday et…”
BackgroundResultInfluentialAutophagy in the presynaptic compartment in health and disease
Vijayan, V., & Verstreken, P. (2017) · The Journal of Cell Biology · doi:10.1083/jcb.201611113 · Cited by 170
“In axons, autophagosomes form continuously at distal tips and contain cargoes derived from synapses (Maday et al., 2012; Maday and Holzbaur, 2014, 2016; Wang et al., 2015).”
BackgroundKuijpers, M., Kochlamazashvili, G., Stumpf, A., Puchkov, D., Swaminathan, A., Lucht, M. T., Krause, E., Maritzen, T., Schmitz, D., & Haucke, V. (2021) · Neuron · doi:10.1016/j.neuron.2020.10.005 · Cited by 170
Selective motor activation in organelle transport along axons
Cason, S. E., & Holzbaur, E. L. F. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00491-w · Cited by 185
Self-citationBoecker, C. A., Goldsmith, J., Dou, D., Cajka, G. G., & Holzbaur, E. L. F. (2021) · Current Biology · doi:10.1016/j.cub.2021.02.061 · Cited by 172
“LRRK2-G2019S enhances recruitment of JIP4 to the AV membrane and increases kinesin activity Both the anterograde motor kinesin and the retrograde motor dynein are bound to AVs; the opposing activities of these motors are regulated by adaptor proteins that inhibit kinesin and promote dynein activity.(21,43) The observe…”
BackgroundSelf-citationReview: Axon pathology in age‐related neurodegenerative disorders
Adalbert, R., & Coleman, M. P. (2012) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2012.01308.x · Cited by 176
Kononenko, N. L., Classen, G. A. E., Kuijpers, M., Puchkov, D., Maritzen, T., Tempes, A., Malik, A. R., Skalecka, A., Bera, S., Jaworski, J., et al. (2017) · Nature Communications · doi:10.1038/ncomms14819 · Cited by 169
Targeting Autophagy for the Treatment of Alzheimer’s Disease: Challenges and Opportunities
Liu, J., & Li, L. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00203 · Cited by 162
Moughamian, A. J., Osborn, G. E., Lazarus, J. E., Maday, S., & Holzbaur, E. L. F. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.0935-13.2013 · Cited by 166
“1B,C), confirming the uniform plus-end outward polarity of the microtubule cytoskeleton in this cell type (Maday et al., 2012).”
BackgroundInfluentialSelf-citationHung, C. O. Y., & Livesey, F. J. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.095 · Cited by 159
“Further maturation of lysosomes requires retrograde transport to the cell soma where luminal proteases can be delivered from the trans-Golgi network efficiently (Maday et al., 2012).”
BackgroundCongenital disorders of autophagy: an emerging novel class of inborn errors of neuro-metabolism
Ebrahimi‐Fakhari, D., Saffari, A., Wahlster, L., Lu, J., Byrne, S., Hoffmann, G. F., Jungbluth, H., & Şahin, M. (2015) · Brain · doi:10.1093/brain/awv371 · Cited by 165
The autophagic roles of Rab small GTPases and their upstream regulators
Szatmári, Z., & Sass, M. (2014) · Autophagy · doi:10.4161/auto.29395 · Cited by 160
Davies, A. K., Itzhak, D. N., Edgar, J. R., Archuleta, T. L., Hirst, J., Jackson, L. P., Robinson, M. S., & Borner, G. H. H. (2018) · Nature Communications · doi:10.1038/s41467-018-06172-7 · Cited by 153
The autophagy gene Wdr45/Wipi4 regulates learning and memory function and axonal homeostasis
Zhao, Y. G., Sun, L., Miao, G., Ji, C., Zhao, H., Sun, H., Miao, L., Yoshii, S. R., Mizushima, N., Wang, X., et al. (2015) · Autophagy · doi:10.1080/15548627.2015.1047127 · Cited by 148
“Autophagy is required for normal axon terminal membrane trafficking and turnover, and plays an essential role in the maintenance of axonal homeostasis and prevention of axonal degeneration.(20,21) Accumulation of axonal spheroid structures in Wdr45 mice indicates that axoN-terminals are more vulnerable to autophagy im…”
BackgroundThe role of mitophagy in the regulation of mitochondrial energetic status in neurons
Han, S., Zhang, M., Jeong, Y. Y., Margolis, D. J., & Cai, Q. (2021) · Autophagy · doi:10.1080/15548627.2021.1907167 · Cited by 151
Degradation of engulfed mitochondria is rate-limiting in Optineurin-mediated mitophagy in neurons
Evans, C. S., & Holzbaur, E. L. (2020) · eLife · doi:10.7554/elife.50260 · Cited by 137
“Autophagosomes mature during trafficking along the axon to the soma by fusion with lysosomes, which leads to efficient cargo degradation (Cheng et al., 2015; Hollenbeck, 1993; Lee et al., 2011; Maday and Holzbaur, 2014; Maday et al., 2012; Neisch et al., 2017).”
BackgroundResultSelf-citationFarfel-Becker, T., Roney, J. C., Cheng, X.-T., Li, S., Cuddy, S. R., & Sheng, Z.-H. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.06.013 · Cited by 152
“Enzymatically Active Degradative Lysosomes Are Positioned in Axons and Distal Tips Although the majority of autophagic and endocytic organelles undergo long-distance retrograde transport fromdistal axons toward the soma, where degradative lysosomes are highly enriched (Cai et al., 2010; Overly et al., 1995; Maday et a…”
InfluentialWang, T., Martin, S., Papadopulos, A., Harper, C. B., Mavlyutov, T. A., Niranjan, D., Glass, N. R., Cooper-White, J. J., Sibarita, J., Choquet, D., et al. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.3757-14.2015 · Cited by 145
Endo‐lysosomal and autophagic dysfunction: a driving factor in Alzheimer's disease?
Whyte, L. S., Lau, A. A., Hemsley, K. M., Hopwood, J. J., & Sargeant, T. J. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.13935 · Cited by 150
“…Gowrishankar et al. (2015) described around the plaque on accumulating vesicles is consistent with work showing autophagic vesicles acquire LAMP1 (from fusion with late endosomes and lysosomes) early in their maturation and transport along the axon to the neuronal cell body (Maday et al. 2012).”
BackgroundXie, Y., Zhou, B., Lin, M.-Y., Wang, S., Foust, K. D., & Sheng, Z.-H. (2015) · Neuron · doi:10.1016/j.neuron.2015.06.026 · Cited by 149
“Since neurons are particularly sensitive to the accumulation of misfolded proteins and damaged organelles, newly formed autophagosomes are eliminated quickly by fusing with endolysosomes, thereby avoiding a buildup of AVs (Maday et al., 2012; Cheng et al., 2015).”
BackgroundAutophagy in axonal and dendritic degeneration
Yang, Y., Coleman, M. P., Zhang, L., Zheng, X., & Yue, Z. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.04.001 · Cited by 146
“Once fully acidified in the proximal part of the axons, autophagosomes may switch to bidirectional motility resembling that of lysosomes [30, 34] and initiate the proteolytic clearance of the autophagy substrates [31] (Figure 1a).”
BackgroundInfluentialRocha, E. M., Smith, G. A., Park, E. Y. H., Cao, H., Graham, A.-R., Brown, E., McLean, J. R., Hayes, M. A., Beagan, J. A., Izen, S. C., et al. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2015.6307 · Cited by 149
“Autophagosome biogenesis typically occurs distally at the axon tip and travels to the cell body using retrograde dynein–dynactin transport (33).”
BackgroundGornstein, E. L., & Schwarz, T. L. (2016) · Experimental Neurology · doi:10.1016/j.expneurol.2016.11.015 · Cited by 145
“Furthermore, secondary to a neurite remodeling defect and retraction, disruption of cellular processes at the distal axon, such as autophagosome formation (Maday et al., 2012) and endocytosis of survival factors (Harrington and Ginty, 2013) could contribute to the pathogenesis.”
BackgroundRegulation of mitochondrial dynamics in astrocytes: Mechanisms, consequences, and unknowns
Jackson, J. G., & Robinson, M. B. (2017) · Glia · doi:10.1002/glia.23252 · Cited by 153
“%) of these autophagosomes contain mitochondrial fragments (Maday et al., 2012), suggesting a constitutive, but low level turnover of mitochondria in neuronal processes.”
BackgroundMacroautophagy in CNS health and disease
Griffey, C. J., & Yamamoto, A. (2022) · Nature reviews. Neuroscience · doi:10.1038/s41583-022-00588-3 · Cited by 147
A role for autophagy in Huntington's disease
Croce, K. R., & Yamamoto, A. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.08.010 · Cited by 144
Niewiadomska, G., Niewiadomski, W., Steczkowska, M., & Gąsiorowska, A. (2021) · Life · doi:10.3390/life11010028 · Cited by 138
Lionaki, E., Markaki, M., Palikaras, K., & Tavernarakis, N. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.04.010 · Cited by 137
“taining dysfunctional or aged mitochondria, has been reported [175].”
BackgroundParkinson's disease: convergence on synaptic homeostasis
Soukup, S., Vanhauwaert, R., & Verstreken, P. (2018) · The EMBO Journal · doi:10.15252/embj.201898960 · Cited by 131
“Autophagy digests parts of the cytoplasm, but at the relatively small presynaptic contacts, where the process is active as well (Maday et al, 2012; Maday & Holzbaur, 2014; Soukup et al, 2016; Oerlundk et al, 2017; Vanhauwaert et al, 2017), it is important to tightly control autophagy as to prevent…”
BackgroundMeasurement of autophagy flux in the nervous system in vivo
Castillo, K., Valenzuela, V, Matus, S., Nassif, M., Oñate, M., Fuentealba, Y., Encina, G., Irrazabal, T., Parsons, G., Court, F. A., et al. (2013) · Cell Death & Disease · doi:10.1038/cddis.2013.421 · Cited by 127
“Autophagosome trafficking along axons was recently described.(31) With this in mind, we monitored the distribution”
BackgroundMethodMechanisms of neuronal homeostasis: Autophagy in the axon
Maday, S. (2016) · Brain Research · doi:10.1016/j.brainres.2016.03.047 · Cited by 130
“Retrogradely moving autophagosomes transport engulfed soluble and organelle cargoes such as ubiquitin and mitochondrial fragments (Maday et al., 2012).”
InfluentialSelf-citationImpaired JIP3-dependent axonal lysosome transport promotes amyloid plaque pathology
Gowrishankar, S., Wu, Y., & Ferguson, S. M. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201612148 · Cited by 138
“This interpretation builds on a growing appreciation that there are high rates of autophagy in the distal regions of axons but that such autophagosomes must fuse with endosomes and acquire lysosomal properties such as acidification before undergoing efficient retrograde back toward the cell body for the eventual degra…”
InfluentialBeckers, J., Tharkeshwar, A. K., & Damme, P. V. (2021) · Autophagy · doi:10.1080/15548627.2021.1872189 · Cited by 132
Mitochondrial Morphology Differences and Mitophagy Deficit in Murine Glaucomatous Optic Nerve
Coughlin, L., Morrison, R. S., Horner, P. J., & Inman, D. M. (2015) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-16126 · Cited by 124
Neuronal vulnerability in Parkinson disease: Should the focus be on axons and synaptic terminals?
Wong, Y. C., Luk, K. C., Purtell, K., Burke, S., Stoessl, A. J., Trudeau, L., Yue, Z., Krainc, D., Oertel, W. H., Obeso, J. A., et al. (2019) · Movement Disorders · doi:10.1002/mds.27823 · Cited by 126
“to the cell body for degradation through the lysosome.(143,182) Aggregated α-syn impairs macroautophagy(125) as does knockdown of α-syn,(183) which indicates that α-syn”
Background
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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