Degradation of engulfed mitochondria is rate-limiting in Optineurin-mediated mitophagy in neurons
Open accessAbstract
Mitophagy, the selective removal of damaged mitochondria, is thought to be critical to maintain neuronal homeostasis. Mutations of proteins in the pathway cause neurodegenerative diseases, suggesting defective mitochondrial turnover contributes to neurodegeneration. In primary rat hippocampal neurons, we developed a mitophagy induction paradigm where mild oxidative stress induced low levels of mitochondrial damage. Mitophagy-associated proteins were sequentially recruited to depolarized mitochondria followed by sequestration into autophagosomes. The localization of these mitophagy events had a robust somal bias. In basal and induced conditions, engulfed mitochondria remained in non-acidified organelles for hours to days, illustrating efficient autophagosome sequestration but delayed lysosomal fusion or acidification. Furthermore, expression of an ALS-linked mutation in the pathway disrupted mitochondrial network integrity and this effect was exacerbated by oxidative stress. Thus, age-related decline in neuronal health or expression of disease-associated mutations in the pathway may exacerbate the slow kinetics of neuronal mitophagy, leading to neurodegeneration.
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The majority of pathogenic OPTN mutations are located in its UBAN domain and may impair ubiquitin binding.
“the majority of pathogenic OPTN mutations are located in its UBAN domain and may impair ubiquitin binding [259]”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [259]
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RETRACTED ARTICLE: Parkin and PINK1 mitigate STING-induced inflammation
Sliter, D. A., Martinez, J., Hao, L., Chen, X., Sun, N., Fischer, T. D., Burman, J. L., Li, Y., Zhang, Z., Narendra, D. P., et al. (2018) · Nature · doi:10.1038/s41586-018-0448-9 · Cited by 1,287 · cited 2× · see citing works
“Interestingly, recent work described an inflammatory phenotype in PINK1 and Parkin KO mice after acute or chronic mitochondrial stress that could be rescued by depletion of a regulator of the type 1 IFN signaling response (Sliter et al., 2018).”
BackgroundInfluentialRetractedFiji: an open-source platform for biological-image analysis
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2019 · Cited by 66,890 · cited 6× · see citing works
“Line scans In Fiji, line scans were generated using a pixel line width to trace OPTN-positive mitochondria and a three-pixel line width to trace axons and dendrites.”
MethodInfluentialRepertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351 · see citing works
Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y., & Shimizu, N. (1998) · Nature · doi:10.1038/33416 · Cited by 5,227 · cited 1× · see citing works
“Mitophagy is primarily regulated by two proteins linked to familial PD, PTEN-Induced Putative Kinase 1 (PINK1) and Parkin (Kitada et al., 1998; Narendra et al., 2008; Narendra et al., 2010b; Valente et al., 2004; Wang and Klionsky, 2011; Youle and Narendra, 2011).”
BackgroundParkin 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 · cited 6× · see citing works
“PINK1 recruits Parkin to phospho-ubiquitinate outer mitochondrial membrane proteins, which act as a specific cue for organelle degradation (Geisler et al., 2010; Kane et al., 2014; Kazlauskaite et al., 2014; Koyano et al., 2014; Matsuda et al., 2010; Narendra et al., 2008; Narendra et al., 2010b; Ordureau et al., 2015…”
BackgroundInfluentialHereditary Early-Onset Parkinson's Disease Caused by Mutations in <i>PINK1</i>
Valente, E. M., Abou-Sleiman, P. M., Caputo, V., Muqit, M. M. K., Harvey, K., Gispert, S., Ali, Z., Del Turco, D., Bentivoglio, A. R., Healy, D. G., et al. (2004) · Science · doi:10.1126/science.1096284 · Cited by 3,481 · cited 1× · see citing works
“Mitophagy is primarily regulated by two proteins linked to familial PD, PTEN-Induced Putative Kinase 1 (PINK1) and Parkin (Kitada et al., 1998; Narendra et al., 2008; Narendra et al., 2010b; Valente et al., 2004; Wang and Klionsky, 2011; Youle and Narendra, 2011).”
BackgroundYoule, R. J., & Narendra, D. P. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3028 · Cited by 3,273 · see citing works
Fission and selective fusion govern mitochondrial segregation and elimination by autophagy
Twig, G., Elorza, A., Molina, A. J. A., Mohamed, H., Wikstrom, J. D., Walzer, G., Stiles, L., Haigh, S. E., Katz, S., Las, G., et al. (2008) · The EMBO Journal · doi:10.1038/sj.emboj.7601963 · Cited by 3,082 · cited 1× · see citing works
“Since rounding and fragmentation are hallmarks of mitochondrial damage (Twig et al., 2008; Westermann, 2010; Youle and Narendra, 2011), we examined morphology following treatments by either staining with tetramethyl rhodamine ethyl ester (TMRE), a vital dye used to measure mitochondrial potential (Figure 1C–D), or by…”
MethodPINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin
Narendra, D. P., Jin, S. M., Tanaka, A., Suen, D.-F., Gautier, C. A., Shen, J., Cookson, M. R., & Youle, R. J. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000298 · Cited by 2,944 · see citing works
The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy
Lazarou, M., Sliter, D. A., Kane, L. A., Sarraf, S. A., Wang, C., Burman, J. L., Sideris, D. P., Fogel, A. I., & Youle, R. J. (2015) · Nature · doi:10.1038/nature14893 · Cited by 2,774 · cited 7× · see citing works
“In non-neuronal cells, OPTN, NDP52, and TAX1BP1 are proposed to mediate the autophagic clearance of damaged mitochondria, while p62 clusters organelles without directly facilitating mitophagy (Heo et al., 2015; Lazarou et al., 2015; Moore and Holzbaur, 2016; Narendra et al., 2010a; Wong and Holzbaur, 2014a).”
BackgroundInfluentialMitochondrial fusion and fission in cell life and death
Westermann, B. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3013 · Cited by 2,002 · cited 2× · see citing works
“Since rounding and fragmentation are hallmarks of mitochondrial damage (Twig et al., 2008; Westermann, 2010; Youle and Narendra, 2011), we examined morphology following treatments by either staining with tetramethyl rhodamine ethyl ester (TMRE), a vital dye used to measure mitochondrial potential (Figure 1C–D), or by…”
MethodMatsuda, N., Sato, S., Shiba, K., Okatsu, K., Saisho, K., Gautier, C. A., Sou, Y.-S., Saiki, S., Kawajiri, S., Sato, F., et al. (2010) · Journal of Cell Biology · doi:10.1083/jcb.200910140 · Cited by 1,969 · cited 1× · see citing works
“PINK1 recruits Parkin to phospho-ubiquitinate outer mitochondrial membrane proteins, which act as a specific cue for organelle degradation (Geisler et al., 2010; Kane et al., 2014; Kazlauskaite et al., 2014; Koyano et al., 2014; Matsuda et al., 2010; Narendra et al., 2008; Narendra et al., 2010b; Ordureau et al., 2015…”
BackgroundDrosophila pink1 is required for mitochondrial function and interacts genetically with parkin
Clark, I. E., Dodson, M. W., Jiang, C., Cao, J. H., Huh, J. R., Seol, J. H., Yoo, S. J., Hay, B. A., & Guo, M. (2006) · Nature · doi:10.1038/nature04779 · Cited by 1,788 · see citing works
Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin
Park, J., Lee, S. B., Lee, S., Kim, Y., Song, S., Kim, S., Bae, E., Kim, J., Shong, M., Kim, J.-M., et al. (2006) · Nature · doi:10.1038/nature04788 · Cited by 1,705 · cited 1× · see citing works
“…contrast, KO rat models of PINK1 exhibited significant dopaminergic neuron loss, and null or mutant flies of PINK1 or Parkin display morphological defects in dopaminergic neurons (Cha et al., 2005; Clark et al., 2006; Dave et al., 2014; Park et al., 2006; Whitworth et al., 2005; Yang et al., 2006).”
BackgroundPINK1-dependent recruitment of Parkin to mitochondria in mitophagy
Vives-Bauza, C., Zhou, C., Huang, Y., Cui, M., de Vries, R. L. A., Kim, J., May, J., Tocilescu, M. A., Liu, W., Ko, H. S., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911187107 · Cited by 1,616 · see citing works
Bellot, G., Garcia-Medina, R., Gounon, P., Chiche, J., Roux, D., Pouysségur, J., & Mazure, N. M. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00166-09 · Cited by 1,501 · see citing works
Ubiquitin is phosphorylated by PINK1 to activate parkin
Koyano, F., Okatsu, K., Kosako, H., Tamura, Y., Go, E., Kimura, M., Kimura, Y., Tsuchiya, H., Yoshihara, H., Hirokawa, T., et al. (2014) · Nature · doi:10.1038/nature13392 · Cited by 1,477 · cited 1× · see citing works
“PINK1 recruits Parkin to phospho-ubiquitinate outer mitochondrial membrane proteins, which act as a specific cue for organelle degradation (Geisler et al., 2010; Kane et al., 2014; Kazlauskaite et al., 2014; Koyano et al., 2014; Matsuda et al., 2010; Narendra et al., 2008; Narendra et al., 2010b; Ordureau et al., 2015…”
BackgroundDissection of Autophagosome Formation Using Apg5-Deficient Mouse Embryonic Stem Cells
Mizushima, N., Yamamoto, A., Hatano, M., Kobayashi, Y., Kabeya, Y., Suzuki, K., Tokuhisa, T., Ohsumi, Y., & Yoshimori, T. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.152.4.657 · Cited by 1,361 · cited 1× · see citing works
“We also observed no significant differences in the expression levels of ATG5 and ATG16L1, proteins required for autophagy initiation (Figure 1—figure supplement 1B-C; Mizushima et al., 2001; Suzuki et al., 2001).”
BackgroundMTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB
Martina, J. A., Chen, Y., Guček, M., & Puertollano, R. (2012) · Autophagy · doi:10.4161/auto.19653 · Cited by 1,360 · cited 15× · see citing works
“Expression of an ALS-associated mutation in OPTN is sufficient to disrupt mitochondrial health under basal conditions and this is exacerbated by oxidative stress.”
BackgroundInfluentialRoczniak-Ferguson, A., Petit, C. S. V., Froehlich, F., Qian, S., Ky, J., Angarola, B. L., Walther, T. C., & Ferguson, S. M. (2012) · Science Signaling · doi:10.1126/scisignal.2002790 · Cited by 1,358 · see citing works
Phosphorylation of the Autophagy Receptor Optineurin Restricts <i>Salmonella</i> Growth
Wild, P., Farhan, H., McEwan, D. G., Wagner, S., Rogov, V. V., Brady, N. R., Richter, B., Korac, J., Waidmann, O., Choudhary, C., et al. (2011) · Science · doi:10.1126/science.1205405 · Cited by 1,298 · see citing works
PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity
Kane, L. A., Lazarou, M., Fogel, A. I., Li, Y., Yamano, K., Sarraf, S. A., Banerjee, S., & Youle, R. J. (2014) · Journal of Cell Biology · doi:10.1083/jcb.201402104 · Cited by 1,298 · cited 1× · see citing works
“…Parkin to phospho-ubiquitinate outer mitochondrial membrane proteins, which act as a specific cue for organelle degradation (Geisler et al., 2010; Kane et al., 2014; Kazlauskaite et al., 2014; Koyano et al., 2014; Matsuda et al., 2010; Narendra et al., 2008; Narendra et al., 2010b; Ordureau et…”
BackgroundMutations of optineurin in amyotrophic lateral sclerosis
Maruyama, H., Morino, H., Ito, H., Izumi, Y., Kato, H., Watanabe, Y., Kinoshita, Y., Kamada, M., Nodera, H., Suzuki, H., et al. (2010) · Nature · doi:10.1038/nature08971 · Cited by 1,265 · cited 3× · see citing works
“OPTN is a heterozygous missense mutation identified in both sporadic and familial cases of ALS (Figure 8A; Maruyama and Kawakami, 2013; Maruyama et al., 2010).”
BackgroundCargo recognition and trafficking in selective autophagy
Stolz, A., Ernst, A., & Dikic, I. (2014) · Nature Cell Biology · doi:10.1038/ncb2979 · Cited by 1,207 · cited 1× · see citing works
“Subsequently, microtubule-associated protein light chain 3 (LC3), is targeted to the ubiquitinated mitochondria via the LC3 interacting region (LIR) of OPTN (Stolz et al., 2014; Wild et al., 2011), leading to engulfment of the organelle inside an LC3-positive autophagosome.”
BackgroundPINK1 and Parkin Target Miro for Phosphorylation and Degradation to Arrest Mitochondrial Motility
Wang, X., Winter, D., Ashrafi, G., Schlehe, J. S., Wong, Y. L., Selkoe, D. J., Rice, S. E., Steen, J. A. J., LaVoie, M. J., & Schwarz, T. L. (2011) · Cell · doi:10.1016/j.cell.2011.10.018 · Cited by 1,161 · cited 2× · see citing works
“In addition, several reports have described arrested axonal mitochondrial motility after damage due to the removal of Miro, a mitochondrial motor adaptor protein (Hsieh et al., 2016; Liu et al., 2012; Wang et al., 2011).”
BackgroundBoland, B., Kumar, A., Lee, S., Platt, F. M., Wegiel, J., Yu, W. H., & Nixon, R. A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0800-08.2008 · Cited by 1,119 · see citing works
Adult-Onset Primary Open-Angle Glaucoma Caused by Mutations in Optineurin
Rezaie, T., Child, A. H., Hitchings, R. A., Brice, G. W., MILLER, L. J., Coca‐Prados, M., Héon, E., Krupin, T., Ritch, R. H., Kreutzer, D. L., et al. (2002) · Science · doi:10.1126/science.1066901 · Cited by 1,105 · see citing works
Suzuki, K., Kirisako, T., Kamada, Y., Mizushima, N., Noda, T., & Ohsumi, Y. (2001) · The EMBO Journal · doi:10.1093/emboj/20.21.5971 · Cited by 1,034 · cited 1× · see citing works
“We also observed no significant differences in the expression levels of ATG5 and ATG16L1, proteins required for autophagy initiation (Figure 1—figure supplement 1B-C; Mizushima et al., 2001; Suzuki et al., 2001).”
BackgroundLandscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization
Sarraf, S. A., Raman, M., Guarani, V., Sowa, M. E., Huttlin, E. L., Gygi, S. P., & Harper, J. W. (2013) · Nature · doi:10.1038/nature12043 · Cited by 1,020 · cited 1× · see citing works
“PINK1 recruits Parkin to phospho-ubiquitinate outer mitochondrial membrane proteins, which act as a specific cue for organelle degradation (Geisler et al., 2010; Kane et al., 2014; Kazlauskaite et al., 2014; Koyano et al., 2014; Matsuda et al., 2010; Narendra et al., 2008; Narendra et al., 2010b; Ordureau et al., 2015…”
BackgroundRogov, V., Dötsch, V., Johansen, T., & Kirkin, V. (2014) · Molecular Cell · doi:10.1016/j.molcel.2013.12.014 · Cited by 992 · cited 1× · see citing works
“, 2002), is recruited to the mitochondrial surface where it interacts with ubiquitin through its ubiquitin binding in ABIN and NEMO (UBAN) domain (Gleason et al., 2011; Heo et al., 2015; Lazarou et al., 2015; Moore and Holzbaur, 2016; Rogov et al., 2014; Wild et al., 2011; Wong and Holzbaur, 2014a; Zhu et al., 2007).”
BackgroundParkin-deficient Mice Exhibit Nigrostriatal Deficits but Not Loss of Dopaminergic Neurons
Goldberg, M. S., Fleming, S. M., Palacino, J. J., Cepeda, C., Lam, H. A., Bhatnagar, A., Meloni, E. G., Wu, N., Ackerson, L. C., Klapstein, G. J., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308947200 · Cited by 913 · see citing works
Heo, J.-M., Ordureau, A., Paulo, J. A., Rinehart, J., & Harper, J. W. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.08.016 · Cited by 906 · cited 5× · see citing works
“…to the mitochondrial surface where it interacts with ubiquitin through its ubiquitin binding in ABIN and NEMO (UBAN) domain (Gleason et al., 2011; Heo et al., 2015; Lazarou et al., 2015; Moore and Holzbaur, 2016; Rogov et al., 2014; Wild et al., 2011; Wong and Holzbaur, 2014a; Zhu et al., 2007).”
BackgroundInfluentialWong, Y. C., & Holzbaur, E. L. F. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1405752111 · Cited by 812 · cited 8× · see citing works
“A constitutive pathway for axonal autophagy has been reported in neurons both in vitro (Maday and Holzbaur, 2014; Wong and Holzbaur, 2014b) and in vivo (Neisch et al., 2017; Soukup et al., 2016; Stavoe et al., 2016).”
BackgroundInfluentialSelf-citationParkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65
Kazlauskaite, A., Kondapalli, C., Gourlay, R., Campbell, D. G., Ritorto, M. S., Hofmann, K., Alessi, D. R., Knebel, A., Trost, M., & Muqit, M. M. K. (2014) · Biochemical Journal · doi:10.1042/bj20140334 · Cited by 806 · see citing works
Yang, Y., Gehrke, S., Imai, Y., Huang, Z., Ouyang, Y., Wang, J.-W., Yang, L., Beal, M. F., Vogel, H., & Lu, B. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602493103 · Cited by 798 · cited 1× · see citing works
“…contrast, KO rat models of PINK1 exhibited significant dopaminergic neuron loss, and null or mutant flies of PINK1 or Parkin display morphological defects in dopaminergic neurons (Cha et al., 2005; Clark et al., 2006; Dave et al., 2014; Park et al., 2006; Whitworth et al., 2005; Yang et al., 2006).”
BackgroundNarendra, D. P., Kane, L. A., Hauser, D. N., Fearnley, I. M., & Youle, R. J. (2010) · Autophagy · doi:10.4161/auto.6.8.13426 · Cited by 789 · cited 3× · see citing works
“…cells, OPTN, NDP52, and TAX1BP1 are proposed to mediate the autophagic clearance of damaged mitochondria, while p62 clusters organelles without directly facilitating mitophagy (Heo et al., 2015; Lazarou et al., 2015; Moore and Holzbaur, 2016; Narendra et al., 2010a; Wong and Holzbaur, 2014a).”
BackgroundHaploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia
Freischmidt, A., Wieland, T., Richter, B., Ruf, W., Schaeffer, V., Müller, K., Marroquin, N., Nordin, F., Hübers, A., Weydt, P., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4000 · Cited by 786 · see citing works
Axonal transport deficits and neurodegenerative diseases
Millecamps, S., & Julien, J.-P. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3380 · Cited by 755 · see citing works
Richter, B., Sliter, D. A., Herhaus, L., Stolz, A., Wang, C., Beli, P., Zaffagnini, G., Wild, P., Martens, S., Wagner, S. A., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1523926113 · Cited by 755 · cited 3× · see citing works
“…damage to a mitochondrion, phospho-ubiquitination of outer mitochondrial membrane proteins mediated by PINK1-recruited Parkin increases the abundance of ubiquitin chains, which recruit OPTN and TBK1 to the organelle (Figure 2A; Harper et al., 2018; Ordureau et al., 2018; Richter et al., 2016).”
BackgroundDeciphering the Molecular Signals of PINK1/Parkin Mitophagy
Nguyen, T. N., Padman, B. S., & Lazarou, M. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2016.05.008 · Cited by 732 · see citing works
Sowter, H., Ratcliffe, P. J., Watson, P. H., Greenberg, A. H., & Harris, A. L. (2001) · PubMed · Cited by 711 · see citing works
Sun, N., Yun, J., Liu, J., Malide, D. A., Liu, C., Rovira, I. I., Holmström, K. M., Fergusson, M. M., Yoo, Y. H., Combs, C. A., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.10.009 · Cited by 696 · cited 1× · see citing works
“However, the use of another acid-sensitive mt-Keima probe illustrated insufficiencies in basal mitophagy in dopaminergic neurons of Parkin-deficient flies (Cornelissen et al., 2018; Katayama et al., 2011; Sun et al., 2015).”
BackgroundOrdureau, A., Sarraf, S. A., Duda, D. M., Heo, J., Jedrychowski, M. P., Sviderskiy, V. O., Olszewski, J. L., Koerber, J. T., Xie, T., Beausoleil, S. A., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.09.007 · Cited by 693 · see citing works
Autophagosomes initiate distally and mature during transport toward the cell soma in primary neurons
Maday, S., Wallace, K. E., & Holzbaur, E. L. F. (2012) · Journal of Cell Biology · doi:10.1083/jcb.201106120 · Cited by 681 · cited 2× · see citing works
“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-citationBuilding and decoding ubiquitin chains for mitophagy
Harper, J. W., Ordureau, A., & Heo, J. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.129 · Cited by 668 · cited 2× · see citing works
“The current model suggests that following damage to a mitochondrion, phospho-ubiquitination of outer mitochondrial membrane proteins mediated by PINK1-recruited Parkin increases the abundance of ubiquitin chains, which recruit OPTN and TBK1 to the organelle (Figure 2A; Harper et al., 2018; Ordureau et al., 2018; Richt…”
BackgroundA Sensitive and Quantitative Technique for Detecting Autophagic Events Based on Lysosomal Delivery
Katayama, H., Kogure, T., Mizushima, N., Yoshimori, T., & Miyawaki, A. (2011) · Chemistry & Biology · doi:10.1016/j.chembiol.2011.05.013 · Cited by 650 · see citing works
Cathepsin D—Many functions of one aspartic protease
Beneš, P., Větvička, V., & Fusek, M. (2008) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2008.02.008 · Cited by 640 · see citing works
Basal Mitophagy Occurs Independently of PINK1 in Mouse Tissues of High Metabolic Demand
McWilliams, T. G., Prescott, A. R., Montava-Garriga, L., Ball, G., Singh, F., Barini, E., Muqit, M. M. K., Brooks, S. P., & Ganley, I. G. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.12.008 · Cited by 591 · cited 1× · see citing works
“The use of the acid-sensitive mitoQC mitophagy probe also did not reveal deficits in tissues of high metabolic demand in mice (mitoQC Pink1) or in dopaminergic neurons of PINK1 and Parkin mutant flies (Lee et al., 2018; McWilliams et al., 2018).”
BackgroundThe Use of pHluorins for Optical Measurements of Presynaptic Activity
Sankaranarayanan, S., Angelis, D. A. D., Rothman, J. E., & Ryan, T. A. (2000) · Biophysical Journal · doi:10.1016/s0006-3495(00)76468-x · Cited by 586 · cited 1× · see citing works
“Thus, we could visualize both LAMP1 localization and acidification, as the fluorescence signal of the SEP will quench in acidic environments while the RFP signal will persist (pH <6; Sankaranarayanan et al., 2000).”
BackgroundMitostasis 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 546 · see citing works
Impaired dopamine release and synaptic plasticity in the striatum of PINK1 -deficient mice
Kitada, T., Pisani, A., Porter, D. R., Yamaguchi, H., Tscherter, A., Martella, G., Bonsi, P., Zhang, C., Pothos, E. N., & Shen, J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702717104 · Cited by 541 · cited 1× · see citing works
“PINK1 and Parkin knock-out (KO) mice display mild phenotypes with no dopaminergic neuron loss, a hallmark of PD, implying there are additional compensatory pathways contributing to neuronal mitophagy in vivo (Akundi et al., 2011; Goldberg et al., 2003; Kitada et al., 2007; Perez and Palmiter, 2005).”
Backgroundmito-QC illuminates mitophagy and mitochondrial architecture in vivo
McWilliams, T. G., Prescott, A. R., Allen, G. F. G., Tamjar, J., Munson, M. J., Thomson, C., Muqit, M. M. K., & Ganley, I. G. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201603039 · Cited by 541 · cited 4× · see citing works
“Under these conditions, as we demonstrate in vitro and was previously shown in vivo (Devireddy et al., 2015; McWilliams et al., 2016; Sung et al., 2016), the PINK1/Parkin mitophagy pathway is compartmentally restricted to the soma.”
BackgroundInfluentialLoss of iron triggers PINK1/Parkin‐independent mitophagy
Allen, G. F. G., Toth, R. L., James, J. L., & Ganley, I. G. (2013) · EMBO Reports · doi:10.1038/embor.2013.168 · Cited by 540 · cited 1× · see citing works
“The fluorescence signal of EGFP, but not mCherry, quenches in acidic environments and thus the shift in fluorescence from yellow to red is commonly used to measure the efficiency of mitophagy (Allen et al., 2013; Lee et al., 2018; McWilliams et al., 2016; Rojansky et al., 2016).”
BackgroundAxonal mitochondrial transport and potential are correlated
Miller, K. E., & Sheetz, M. P. (2004) · Journal of Cell Science · doi:10.1242/jcs.01130 · Cited by 512 · see citing works
Ashrafi, G., Schlehe, J. S., LaVoie, M. J., & Schwarz, T. L. (2014) · Journal of Cell Biology · doi:10.1083/jcb.201401070 · Cited by 502 · cited 13× · see citing works
“We hypothesize that either long-term exposure to low doses (>2 hr) or short periods of high concentration of AA (Ashrafi et al., 2014) may disrupt mitochondrial bioenergetics causing axonal mitochondria to undergo mitophagy locally to preserve the health of the neuron.”
BackgroundInfluentialThe PINK1-Parkin pathway promotes both mitophagy and selective respiratory chain turnover in vivo
Vincow, E. S., Merrihew, G., Thomas, R. E., Shulman, N. J., Beyer, R. P., MacCoss, M. J., & Pallanck, L. J. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1221132110 · Cited by 478 · cited 1× · see citing works
“Further, stable isotope labeling of flies showed a slowing in the turnover of mitochondrial proteins isolated from the heads of Parkin null flies (Vincow et al., 2013).”
BackgroundParkin-deficient mice are not a robust model of parkinsonism
Perez, F. A., & Palmiter, R. D. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409598102 · Cited by 477 · see citing works
Lee, S., Satō, Y., & Nixon, R. A. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.6412-10.2011 · Cited by 471 · cited 3× · see citing works
“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).”
BackgroundResultHsieh, C.-H., Shaltouki, A., Gonzalez, A. E., da Cruz, A. B., Burbulla, L. F., Lawrence, E. S., Schüle, B., Krainc, D., Palmer, T. D., & Wang, X. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.08.002 · Cited by 459 · see citing works
The Mitochondrial Fusion-Promoting Factor Mitofusin Is a Substrate of the PINK1/Parkin Pathway
Poole, A. C., Thomas, R. E., Yu, S., Vincow, E. S., & Pallanck, L. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010054 · Cited by 440 · cited 1× · see citing works
“…for organelle degradation (Geisler et al., 2010; Kane et al., 2014; Kazlauskaite et al., 2014; Koyano et al., 2014; Matsuda et al., 2010; Narendra et al., 2008; Narendra et al., 2010b; Ordureau et al., 2015; Ordureau et al., 2014; Poole et al., 2010; Sarraf et al., 2013; VivesBauza et al., 2010).”
Dynein-dependent Movement of Autophagosomes Mediates Efficient Encounters with Lysosomes
Kimura, S., Noda, T., & Yoshimori, T. (2008) · Cell Structure and Function · doi:10.1247/csf.08005 · Cited by 436 · cited 1× · see citing works
“These data are consistent with previous reports that autophagosomes effectively fuse with lysosomes to degrade cargo (Boland et al., 2008; Kimura et al., 2008; Lee et al., 2011; Maday et al., 2012).”
ResultWhitworth, A. J., Theodore, D. A., Greene, J. C., Beneš, H., Wes, P. D., & Pallanck, L. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501078102 · Cited by 421 · see citing works
Mitochondrial trafficking and anchoring in neurons: New insight and implications
Sheng, Z. (2014) · The Journal of Cell Biology · doi:10.1083/jcb.201312123 · Cited by 409 · see citing works
Mitochondria removal by autophagy
Wang, K., & Klionsky, D. J. (2011) · Autophagy · doi:10.4161/auto.7.3.14502 · Cited by 407 · see citing works
Wong, Y. C., & Holzbaur, E. L. F. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1870-13.2014 · Cited by 395 · see citing works
Self-citationAutophagosome 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 · see citing works
Self-citationLiu, S., Sawada, T., Lee, S., Yu, W., Silverio, G., Alapatt, P., Millan, I., Shen, A., Saxton, W., Kanao, T., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002537 · Cited by 371 · cited 2× · see citing works
“, 2014) and studies indicating that axonal mitochondria motility is arrested following mitochondrial damage (Hsieh et al., 2016; Liu et al., 2012; Wang et al., 2011), necessitating a local clearance mechanism.”
BackgroundMoore, A. S., & Holzbaur, E. L. F. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1523810113 · Cited by 351 · cited 9× · see citing works
“First, OPTNE478G fails to translocate to damaged organelles, which may perturb the mitophagy pathway in a dominant-negative manner (Moore and Holzbaur, 2016).”
BackgroundInfluentialSelf-citationBasal mitophagy is widespread in Drosophila but minimally affected by loss of Pink1 or parkin
Lee, J. J., Sánchez-Martínez, Á., Martinez, A., Benincá, C., Mayor, U., Clague, M. J., & Whitworth, A. J. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201801044 · Cited by 343 · cited 2× · see citing works
“The fluorescence signal of EGFP, but not mCherry, quenches in acidic environments and thus the shift in fluorescence from yellow to red is commonly used to measure the efficiency of mitophagy (Allen et al., 2013; Lee et al., 2018; McWilliams et al., 2016; Rojansky et al., 2016).”
BackgroundRojansky, R. B., Cha, M.-Y., & Chan, D. C. (2016) · eLife · doi:10.7554/elife.17896 · Cited by 337 · cited 1× · see citing works
“The fluorescence signal of EGFP, but not mCherry, quenches in acidic environments and thus the shift in fluorescence from yellow to red is commonly used to measure the efficiency of mitophagy (Allen et al., 2013; Lee et al., 2018; McWilliams et al., 2016; Rojansky et al., 2016).”
BackgroundUbiquitin-independent function of optineurin in autophagic clearance of protein aggregates
Korac, J., Schaeffer, V., Kovacevic, I., Clement, A. M., Jungblut, B., Behl, C., Terzic, J., & Dikic, I. (2013) · Journal of Cell Science · doi:10.1242/jcs.114926 · Cited by 336 · cited 1× · see citing works
“These puncta may represent either the self-association of OPTN or the recruitment of OPTN to other autophagy substrates, such as protein aggregates (Korac et al., 2013).”
BackgroundCai, Q., Zakaria, H. M., Simone, A., & Sheng, Z. (2012) · Current Biology · doi:10.1016/j.cub.2012.02.005 · Cited by 332 · cited 7× · see citing works
“DOI: https://doi.org/10.7554/eLife.50260 2 of 30 inhibitor) displayed enhanced retrograde mitochondrial motility, suggesting damaged organelles are trafficked back to the soma for degradation (Cai et al., 2012; Miller and Sheetz, 2004).”
InfluentialYun, J., Puri, R., Yang, H. M., Lizzio, M. A., Wu, C., Sheng, Z., & Guo, M. (2014) · eLife · doi:10.7554/elife.01958 · Cited by 325 · see citing works
Pottier, C., Bieniek, K. F., Finch, N., van de Vorst, M., Baker, M., Perkersen, R., Brown, P., Ravenscroft, T., van Blitterswijk, M., Nicholson, A. M., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1436-x · Cited by 312 · see citing works
The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations
Geisler, S., Holmström, K. M., Treis, A., Skujat, D., Weber, S. S., Fiesel, F. C., Kahle, P. J., & Springer, W. (2010) · Autophagy · doi:10.4161/auto.6.7.13286 · Cited by 311 · cited 1× · see citing works
“PINK1 recruits Parkin to phospho-ubiquitinate outer mitochondrial membrane proteins, which act as a specific cue for organelle degradation (Geisler et al., 2010; Kane et al., 2014; Kazlauskaite et al., 2014; Koyano et al., 2014; Matsuda et al., 2010; Narendra et al., 2008; Narendra et al., 2010b;…”
BackgroundOrdureau, A., Heo, J.-M., Duda, D. M., Paulo, J. A., Olszewski, J. L., Yanishevski, D., Rinehart, J., Schulman, B. A., & Harper, J. W. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1506593112 · Cited by 310 · see citing works
Compartment-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 · see citing works
Self-citationHollenbeck, P. J. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.121.2.305 · Cited by 295 · cited 1× · see citing works
“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).”
BackgroundA LRRK2-Dependent EndophilinA Phosphoswitch Is Critical for Macroautophagy at Presynaptic Terminals
Soukup, S., Kuenen, S., Vanhauwaert, R., Manetsberger, J., Hernández-Díaz, S., Swerts, J., Schoovaerts, N., Vilain, S., Gounko, N. V., Vints, K., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.09.037 · Cited by 285 · cited 1× · see citing works
“A constitutive pathway for axonal autophagy has been reported in neurons both in vitro (Maday and Holzbaur, 2014; Wong and Holzbaur, 2014b) and in vivo (Neisch et al., 2017; Soukup et al., 2016; Stavoe et al., 2016).”
BackgroundZhu, G., Wu, C.-J., Zhao, Y., & Ashwell, J. D. (2007) · Current Biology · doi:10.1016/j.cub.2007.07.041 · Cited by 282 · see citing works
Lysosome 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 265 · see citing works
Characterization of LAMP1-labeled nondegradative lysosomal and endocytic compartments in neurons
Cheng, X., Xie, Y., Zhou, B., Huang, N., Farfel‐Becker, T., & Sheng, Z. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201711083 · Cited by 264 · see citing works
Parkin negatively regulates JNK pathway in the dopaminergic neurons of Drosophila
Cha, G., Kim, S., Park, J., Lee, E., Kim, M., Lee, S. B., Kim, J., Chung, J., & Cho, K. S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500346102 · Cited by 261 · see citing works
Axonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes
Cheng, X., Zhou, B., Lin, M.-Y., Cai, Q., & Sheng, Z. (2015) · The Journal of Cell Biology · doi:10.1083/jcb.201412046 · Cited by 252 · cited 1× · see citing works
“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).”
BackgroundThe Role of Mitophagy in Innate Immunity
Gkikas, I., Palikaras, K., & Tavernarakis, N. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01283 · Cited by 244 · see citing works
Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila
Cornelissen, T., Vilain, S., Vints, K., Gounko, N., Verstreken, P., & Vandenberghe, W. (2018) · eLife · doi:10.7554/elife.35878 · Cited by 239 · cited 1× · see citing works
“However, the use of another acid-sensitive mt-Keima probe illustrated insufficiencies in basal mitophagy in dopaminergic neurons of Parkin-deficient flies (Cornelissen et al., 2018; Katayama et al., 2011; Sun et al., 2015).”
BackgroundBORC/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 · cited 2× · see citing works
“DOI: https://doi.org/10.7554/eLife.50260 20 of 30 was generated from site-directed mutagenesis, untagged-Parkin (mCherry-Parkin was removed), YFP-NavII-III (Addgene 26056), GFP-Ub (Addgene 11928), TBK1 (Addgene 23851) was recloned into a pSNAPf vector (New England Biolabs), LAMP1-EGFP was subcloned from Addgene 1817 w…”
MethodInfluentialPhenotypic characterization of recessive gene knockout rat models of Parkinson's disease
Dave, K. D., Silva, S., Sheth, N. P., Ramboz, S., Beck, M. J., Quang, C., Switzer, R. C., Ahmad, S. O., Sunkin, S. M., Walker, D., et al. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.06.009 · Cited by 222 · see citing works
Sriram, S. R., Li, X., Ko, H. S., Chung, K. K. K., Wong, E. S. P., Lim, K. L., Dawson, V. L., & Dawson, T. M. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi292 · Cited by 221 · cited 1× · see citing works
“Only partial rescue was observed with the Parkinson’s disease-linked mutant mCherry-Parkin (Sriram et al., 2005).”
BackgroundKIF1A/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 · see citing works
ROS-dependent regulation of Parkin and DJ-1 localization during oxidative stress in neurons
Joselin, A. P., Hewitt, S. J., Callaghan, S. M., Kim, R. H., Chung, Y.-H., Mak, T. W., Shen, J., Slack, R. S., & Park, D. S. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds325 · Cited by 205 · see citing works
Koentjoro, B., Park, J.-S., & Sue, C. M. (2017) · Scientific Reports · doi:10.1038/srep44373 · Cited by 191 · cited 1× · see citing works
“, 2019) and NIX/BNIP3L-dependent mitophagy (Bellot et al., 2009; Koentjoro et al., 2017; Real et al., 2005; Sowter et al., 2001) support mitochondrial clearance.”
BackgroundAkundi, R. S., Huang, Z., Eason, J., Pandya, J. D., Zhi, L., Cass, W. A., Sullivan, P. G., & Büeler, H. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016038 · Cited by 187 · see citing works
Ordureau, A., Paulo, J. A., Zhang, W., Ahfeldt, T., Zhang, J., Cohn, E. F., Hou, Z., Heo, J., Rubin, L. L., Sidhu, S. S., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.03.012 · Cited by 184 · see citing works
Autophagy 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 178 · see citing works
Self-citationGleason, C. E., Ordureau, A., Gourlay, R., Arthur, J. S. C., & Cohen, P. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.267567 · Cited by 173 · cited 1× · see citing works
“…2002), is recruited to the mitochondrial surface where it interacts with ubiquitin through its ubiquitin binding in ABIN and NEMO (UBAN) domain (Gleason et al., 2011; Heo et al., 2015; Lazarou et al., 2015; Moore and Holzbaur, 2016; Rogov et al., 2014; Wild et al., 2011; Wong and Holzbaur,…”
BackgroundNIPSNAP1 and NIPSNAP2 Act as “Eat Me” Signals for Mitophagy
Abudu, Y. P., Pankiv, S., Mathai, B. J., Lystad, A. H., Bindesbøll, C., Brenne, H. B., Ng, M. Y. W., Thiede, B., Yamamoto, A., Nthiga, T. M., et al. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.03.013 · Cited by 160 · see citing works
Mul1 restrains Parkin-mediated mitophagy in mature neurons by maintaining ER-mitochondrial contacts
Puri, R., Cheng, X., Lin, M.-Y., Huang, N., & Sheng, Z. (2019) · Nature Communications · doi:10.1038/s41467-019-11636-5 · Cited by 155 · cited 1× · see citing works
“Previous studies have proposed that mitochondrial ubiquitin ligase 1 (MUL1) plays a role in mitochondrial quality control in neurons, where it functions as an additional E3 ubiquitin ligase in a parallel pathway to Parkin (Ambivero et al., 2014; Puri et al., 2019; Yun et al., 2014).”
BackgroundLysosome biogenesis in health and disease
Bajaj, L., Lotfi, P., Pal, R., Ronza, A. D., Sharma, J., & Sardiello, M. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14564 · Cited by 153 · see citing works
Sardiello, M. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13131 · Cited by 135 · cited 1× · see citing works
“In addition, we monitored expression level of Transcription Factor EB (TFEB), a master transcriptional regulator of genes that are involved in lysosomal biogenesis and function (Bajaj et al., 2019; Sardiello, 2016).”
MethodDegradation of dendritic cargos requires Rab7-dependent transport to somatic lysosomes
Yap, C. C., Digilio, L. C., McMahon, L. P., Garcia, A. D. R., & Winckler, B. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201711039 · Cited by 135 · cited 1× · see citing works
“…LAMP1 is routinely used as a marker of lysosomes, recent work has demonstrated that a portion of LAMP1-positive organelles did not colocalize with lysosomal hydrolases, implying not all LAMP1 is on degradation-competent vesicles but also on late endosomes (Cheng et al., 2018; Yap et al., 2018).”
BackgroundDegradation of Alzheimer's amyloid fibrils by microglia requires delivery of ClC-7 to lysosomes
Majumdar, A., Capetillo‐Zarate, E., Cruz, D. L., Gouras, G. K., & Maxfield, F. R. (2011) · Molecular Biology of the Cell · doi:10.1091/mbc.e10-09-0745 · Cited by 106 · cited 1× · see citing works
“Alternatively, ion transporters or other proteins associated with this vesicular compartment could be differentially regulated (Majumdar et al., 2011), but further work will be required to determine the underlying cause.”
BackgroundNeisch, A. L., Neufeld, T. P., & Hays, T. S. (2017) · The Journal of Cell Biology · doi:10.1083/jcb.201606082 · Cited by 103 · cited 2× · see citing works
“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).”
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 92 · see citing works
Ambivero, C. T., Cilenti, L., Main, S., & Zervos, A. S. (2014) · Cellular Signalling · doi:10.1016/j.cellsig.2014.09.004 · Cited by 84 · cited 1× · see citing works
“Previous studies have proposed that mitochondrial ubiquitin ligase 1 (MUL1) plays a role in mitochondrial quality control in neurons, where it functions as an additional E3 ubiquitin ligase in a parallel pathway to Parkin (Ambivero et al., 2014; Puri et al., 2019; Yun et al., 2014).”
BackgroundSung, H., Tandarich, L. C., Nguyen, K. K., & Hollenbeck, P. J. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.0633-16.2016 · Cited by 83 · cited 5× · see citing works
“The spatial specificity of mitophagy was previously postulated based on observations in vivo in Drosophila (Devireddy et al., 2015; Sung et al., 2016), qualitative findings of acidified mitochondria only within the soma in mito-QC mice (McWilliams et al.”
BackgroundInfluentialDevireddy, S., Liu, A., Lampe, T., & Hollenbeck, P. J. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.1198-15.2015 · Cited by 77 · cited 5× · see citing works
“…of mitophagy in PINK1 or Parkin mutant flies found no enhanced accumulation of axonal mitochondria in motor neurons, but did report dramatic changes in the morphology of somal mitochondria, indicating neuronal mitophagy may be compartmentally restricted (Devireddy et al., 2015; Sung et al., 2016).”
BackgroundInfluentialKim, Y. Y., Um, J., Yoon, J.-H., Kim, H., Lee, D.-Y., Lee, Y., Jee, H., Kim, Y. M., Jang, J. S., Jang, Y.-G., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201900073r · Cited by 73 · see citing works
Real, P. J., Benito, A., Cuevas, J., Berciano, M. T., Juan, A. D., Coffer, P. J., Gómez‐Román, J., Lafarga, M., López-Vega, J. M., & Fernández-Luna, J. L. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-1134 · Cited by 72 · cited 1× · see citing works
“…studies have suggested that alternative pathways such as NIPSNAP/Parkin-mediated mitophagy (Nautiyal et al., 2010; Princely Abudu et al., 2019) and NIX/BNIP3L-dependent mitophagy (Bellot et al., 2009; Koentjoro et al., 2017; Real et al., 2005; Sowter et al., 2001) support mitochondrial clearance.”
BackgroundClinicopathologic study on an ALS family with a heterozygous E478G optineurin mutation
Ito, H., Nakamura, M., Komure, O., Ayaki, T., Wate, R., Maruyama, H., Nakamura, Y., Fujita, K., Kaneko, S., Okamoto, Y., et al. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0842-y · Cited by 61 · cited 1× · see citing works
“Expression of an ALS-associated OPTN mutant increases the neurons susceptibility to stress and damage Genetic studies have identified mutations in OPTN as causative for ALS and frontotemporal dementia (FTD; Ito et al., 2011; Maruyama and Kawakami, 2013; Pottier et al., 2015).”
BackgroundOptineurin and amyotrophic lateral sclerosis
Maruyama, H., & Kawakami, H. (2012) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/ggi.12022 · Cited by 50 · cited 3× · see citing works
“OPTN is a heterozygous missense mutation identified in both sporadic and familial cases of ALS (Figure 8A; Maruyama and Kawakami, 2013; Maruyama et al., 2010).”
BackgroundNeuronal localization of the mitochondrial protein NIPSNAP1 in rat nervous system
Nautiyal, M., Sweatt, A. J., MacKenzie, J. A., Payne, R. M., Szucs, S., Matalon, R. K., Wallin, R., & Hutson, S. M. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07326.x · Cited by 27 · cited 1× · see citing works
“Other studies have suggested that alternative pathways such as NIPSNAP/Parkin-mediated mitophagy (Nautiyal et al., 2010; Princely Abudu et al., 2019) and NIX/BNIP3L-dependent mitophagy (Bellot et al., 2009; Koentjoro et al., 2017; Real et al., 2005; Sowter et al., 2001) support mitochondrial…”
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The mechanisms and roles of selective autophagy in mammals
Vargas, J. N. S., Hamasaki, M., Kawabata, T., Youle, R. J., & Yoshimori, T. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00542-2 · Cited by 1,030 · see citing works
Mitochondria ROS and mitophagy in acute kidney injury
Su, L., Zhang, J., Gomez, H., Kellum, J. A., & Peng, Z. (2022) · Autophagy · doi:10.1080/15548627.2022.2084862 · Cited by 810 · see citing works
The role of PINK1–Parkin in mitochondrial quality control
Narendra, D. P., & Youle, R. J. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01513-9 · Cited by 580 · see citing works
“In cultured cells, acidification and degradation of mitochondria in the soma may be rate-limiting steps, suggesting that neurons may have comparatively low rates of mitophagic flux 137 .”
Quality control of the mitochondrion
Ng, M. Y. W., Wai, T., & Simonsen, A. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.02.009 · Cited by 453 · see citing works
Defective mitophagy in Alzheimer’s disease
Pradeepkiran, J. A., & Reddy, P. H. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101191 · Cited by 367 · see citing works
“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript mitochondrial content determines the markers of mitochondrial quality (Evans and Holzbaur, 2020; Calkins et al., 2011; Wang et al., 2009).”
BackgroundProgramming axonal mitochondrial maintenance and bioenergetics in neurodegeneration and regeneration
Cheng, X., Huang, N., & Sheng, Z. (2022) · Neuron · doi:10.1016/j.neuron.2022.03.015 · Cited by 253 · see citing works
Autophagy 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 · see citing works
BNIP3L/NIX-mediated mitophagy protects against glucocorticoid-induced synapse defects
Choi, G. E., Lee, H. J., Chae, C. W., Cho, J. H., Jung, Y. H., Kim, J. S., Kim, S. Y., Lim, J. R., & Han, H. J. (2021) · Nature Communications · doi:10.1038/s41467-020-20679-y · Cited by 182 · see citing works
Mitochondrial quality control in human health and disease
Liu, B., Xu, C.-Z., Liu, Y., Lu, Z., Fu, T.-L., Li, G., Deng, Y., Luo, G., Ding, S. Z., Li, N., et al. (2024) · Military Medical Research · doi:10.1186/s40779-024-00536-5 · Cited by 189 · see citing works
Borcherding, N. C., Jia, W., Giwa, R., Field, R. L., Moley, J. R., Kopecky, B. J., Chan, M. M., Yang, B. Q., Sabio, J. M., Walker, E. C., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.08.010 · Cited by 174 · see citing works
Boecker, 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 166 · see citing works
Self-citationTargeting mitophagy in neurodegenerative diseases
Antico, O., Thompson, P. W., Hertz, N. T., Muqit, M. M. K., & Parton, L. E. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01105-0 · Cited by 178 · see citing works
“Although most mitochondria are distributed in the distal neuronal compartments 5 , mitophagy in neurons has been detected mainly in the soma (cell bodies), correlating with where the majority of active lys osomes are situated 80–83 .”
Eapen, V. V., Swarup, S., Hoyer, M., Paulo, J. A., & Harper, J. W. (2021) · eLife · doi:10.7554/elife.72328 · Cited by 162 · see citing works
Neuronal autophagy and mitophagy in Parkinson's disease
Lizama, B. N., & Chu, C. T. (2021) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2021.100972 · Cited by 149 · see citing works
Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response
Ashrafizadeh, M., Paskeh, M. D. A., Mirzaei, S., Gholami, M. H., Zarrabi, A., Hashemi, F., Hushmandi, K., Hashemi, M., Nabavi, N., Crea, F., et al. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02293-6 · Cited by 147 · see citing works
Emerging views of OPTN (optineurin) function in the autophagic process associated with disease
Qiu, Y., Wang, J., Li, H., Yang, B., Wang, J., He, Q., & Weng, Q. (2021) · Autophagy · doi:10.1080/15548627.2021.1908722 · Cited by 139 · see citing works
Motor proteins at the mitochondria–cytoskeleton interface
Kruppa, A. J., & Buß, F. (2021) · Journal of Cell Science · doi:10.1242/jcs.226084 · Cited by 121 · see citing works
The multifaceted role of mitochondria in autism spectrum disorder
Халиулин, И. Г., Hamoudi, W., & Amal, H. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02725-z · Cited by 122 · see citing works
“This results in the translocation of Parkin to the mitochondria and initiation of mitochondrial degradation [322, 323], which helps to maintain neuronal homeostasis [324].”
Agujetas, V. R., Barbero‐Camps, E., de Dios, C., Podlesniy, P., Abadin, X., Morales, A., Marı́, M., Trullás, R., & Colell, A. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00435-6 · Cited by 110 · see citing works
“This apparent discrepancy may be likely related to the inducer used and the speci c time course of mitophagy in neurons, which is longer compared with non-neuronal cells [68, 69].”
Goldsmith, J., Ordureau, A., Harper, J. W., & Holzbaur, E. L. F. (2022) · Neuron · doi:10.1016/j.neuron.2021.12.029 · Cited by 105 · see citing works
Self-citationAgarwal, S., & Muqit, M. M. K. (2021) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2021.09.005 · Cited by 103 · see citing works
ALS- and FTD-associated missense mutations in TBK1 differentially disrupt mitophagy
Harding, O. J., Evans, C. S., Ye, J., Cheung, J., Maniatis, T., & Holzbaur, E. L. F. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2025053118 · Cited by 96 · see citing works
Self-citationGlucocorticoid impairs mitochondrial quality control in neurons
Choi, G. E., & Han, H. J. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105301 · Cited by 95 · see citing works
Lie, P. P. Y., Yang, D., Stavrides, P. H., 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 87 · see citing works
“, 2010), and LAMP1 acquisition by autophagosomes is temporally separate from acidification (Evans and Holzbaur, 2020).”
BackgroundMechanisms underlying ubiquitin-driven selective mitochondrial and bacterial autophagy
Goodall, E. A., Kraus, F., & Harper, J. W. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.03.012 · Cited by 85 · see citing works
Phospholipase D3 degrades mitochondrial DNA to regulate nucleotide signaling and APP metabolism
Acker, Z. P. V., Perdok, A., Hellemans, R., North, K., Vorsters, I., Cappel, C. C., Dehairs, J., Swinnen, J. V., Sannerud, R., Bretou, M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38501-w · Cited by 69 · see citing works
“The latter may be particularly relevant to neurons with their high energetic activity and associated high mitochondrial turnover 43 .”
Antico, O., Ordureau, A., Stevens, M., Singh, F., Nirujogi, R. S., Gierliński, M., Barini, E., Rickwood, M. L., Prescott, A. R., Toth, R. L., et al. (2021) · Science Advances · doi:10.1126/sciadv.abj0722 · Cited by 63 · see citing works
“…the autophagy receptor proteins NDP52, p62, OPTN, Tax1bp, and Next to BRCA1 gene 1 protein (NBR1), and several studies suggests that NDP52 and OPTN are the main ubiquitin-dependent receptors for efficient mitophagic clearance of damaged mitochondria both in HeLa cells and neurons ( 23 , 24 , 49 ).”
Wrighton, P. J., Shwartz, A., Heo, J., Quenzer, E. D., LaBella, K. A., Harper, J. W., & Goessling, W. (2021) · Journal of Cell Science · doi:10.1242/jcs.256255 · Cited by 62 · see citing works
Rojas-Charry, L., Nardi, L., Methner, A., & Schmeißer, M. J. (2020) · Journal of Molecular Medicine · doi:10.1007/s00109-020-02018-2 · Cited by 59 · see citing works
Role of Autophagy Pathway in Parkinson’s Disease and Related Genetic Neurological Disorders
Themistokleous, C., Bagnoli, E., Parulekar, R., & Muqit, M. M. K. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.168144 · Cited by 49 · see citing works
Giovedı̀, S., Ravanelli, M. M., Parisi, B., Bettegazzi, B., & Guarnieri, F. C. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.602116 · Cited by 49 · see citing works
“Similarly, ALS-linked mutations in optineurin interfere with the clearance of protein inclusions and of damaged mitochondria in cell lines and neurons (Wong and Holzbaur, 2014b; Shen et al., 2015; Evans and Holzbaur, 2020).”
BackgroundNeuronal Mitophagy: Friend or Foe?
Doxaki, C., & Palikaras, K. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.611938 · Cited by 46 · see citing works
Impaired Mitophagy in Neurons and Glial Cells during Aging and Age-Related Disorders
Sukhorukov, V. S., Воронков, Д. Н., Baranich, T. I., Mudzhiri, N. M., Magnaeva, A., & Illarioshkin, S. N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910251 · Cited by 50 · see citing works
Decreasing pdzd8-mediated mito–ER contacts improves organismal fitness and mitigates Aβ 42 toxicity
Hewitt, V. L., Miller‐Fleming, L., Twyning, M. J., Andreazza, S., Mattedi, F., Prudent, J., Polleux, F., Vagnoni, A., & Whitworth, A. J. (2022) · Life Science Alliance · doi:10.26508/lsa.202201531 · Cited by 44 · see citing works
Organization of the autophagy pathway in neurons
Sidibe, D. K., Vogel, M. C., & Maday, S. (2022) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2022.102554 · Cited by 38 · see citing works
Mitophagy and Neurodegeneration: Between the Knowns and the Unknowns
Jetto, C. T., Nambiar, A., & Manjithaya, R. R. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.837337 · Cited by 44 · see citing works
Li, H., Doric, Z., Berthet, A., Jorgens, D. M., Nguyen, M. K., Hsieh, I., Margulis, J., Fang, R., Debnath, J., Sesaki, H., et al. (2021) · Science Advances · doi:10.1126/sciadv.abf6580 · Cited by 42 · see citing works
“Notably, these findings differ from those of a recent study that used LysoTracker, superecliptic pHluorin (SEP)–LAMP1-RFP, and mitochondria-targeted EGFP-mCherry reporters to conclude that mitochondrial acidification is a very slow process that takes several hours following mitophagosome formation and LAMP1 accumulati…”
ResultZaninello, M., Palikaras, K., Sotiriou, A., Tavernarakis, N., & Scorrano, L. (2021) · Cell Death and Differentiation · doi:10.1038/s41418-021-00847-3 · Cited by 40 · see citing works
Mitophagy in Neurons: Mechanisms Regulating Mitochondrial Turnover and Neuronal Homeostasis
Basak, B., & Holzbaur, E. L. F. (2025) · Journal of Molecular Biology · doi:10.1016/j.jmb.2025.169161 · Cited by 44 · see citing works
Self-citationRole of mitophagy in the neurodegenerative diseases and its pharmacological advances: A review
Wang, Q., Xue, H., Yue, Y., Hao, S., Huang, S., & Zhang, Z. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.1014251 · Cited by 38 · see citing works
“Interestingly, OPTN-mediated mitophagy appears to be spatially confined to neuronal cell bodies, with just a few mitophagy events observed in axons or dendrites (Evans and Holzbaur, 2020).”
BackgroundPARK15/FBXO7 is dispensable for PINK1/Parkin mitophagy in iNeurons and HeLa cell systems
Kraus, F., Goodall, E. A., Smith, I. R. L., Jiang, Y., Paoli, J. C., Adolf, F., Zhang, J., Paulo, J. A., Schulman, B. A., & Harper, J. W. (2023) · EMBO Reports · doi:10.15252/embr.202256399 · Cited by 35 · see citing works
“…recruitment of selective autophagy cargo receptors including OPTN, CALCOCO2 (also called NDP52), and SQSTM1 (also called p62) to facilitate the assembly of an autophagosome around the ubiquitylated organelle (Wong & Holz-baur, 2014; Heo et al , 2015; Lazarou et al , 2015; Evans & Holzbaur, 2020).”
Hallmarks and Molecular Tools for the Study of Mitophagy in Parkinson’s Disease
Goiran, T., Eldeeb, M. A., Zorca, C. E., & Fon, E. A. (2022) · Cells · doi:10.3390/cells11132097 · Cited by 38 · see citing works
Mitophagy in relation to chronic inflammation/ROS in aging
Kong, L., Li, S., Fu, Y., Cai, Q., Du, X., Liang, J., & Ma, T. (2024) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-024-05042-9 · Cited by 36 · see citing works
“Mitophagy restricts mtROS production, by removing aging and damaged mitochondria, hindering the progression of this process [89].”
Liu, W., Ren, Y., Wang, T., Wang, M., Xu, Y., Zhang, J., Bi, J., Wu, Z., Zhang, Y., & Wu, R. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-01923-6 · Cited by 33 · see citing works
“These results reveal a novel CIRP-mediated acute pancreatitis injury pathway and provide a new target for future treatment.”
BackgroundMethodUpregulated pexophagy limits the capacity of selective autophagy
Germain, K., So, R. W. L., DiGiovanni, L. F., Watts, J. C., Bandsma, R., & Kim, P. K. (2024) · Nature Communications · doi:10.1038/s41467-023-44005-4 · Cited by 32 · see citing works
Optineurin-facilitated axonal mitochondria delivery promotes neuroprotection and axon regeneration
Liu, D., Webber, H. C., Bian, F., Xu, Y., Prakash, M., Feng, X., Yang, M., Yang, H., You, I.-J., Li, L., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-57135-8 · Cited by 34 · see citing works
“The OPTN E478G mutant found in ALS patients loses the interaction between the OPTN UBAN domain and ubiquitinated cargos, which disrupts mitophagy and causes cell death in cultured neurons 59 .”
Shen, J., Xie, P., Wang, J., Yang, F., Li, S., Jiang, H., Wu, X., Zhou, F., & Li, J. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103196 · Cited by 31 · see citing works
“Typically, mitophagy contributes to neuronal cell viability and offers protection through various mechanisms, including the removal of damaged mitochondria, which are primary sources of ROS production [51,52].”
BackgroundSelective Autophagy in Hyperglycemia-Induced Microvascular and Macrovascular Diseases
Bharath, L. P., Rockhold, J. D., & Conway, R. (2021) · Cells · doi:10.3390/cells10082114 · Cited by 31 · see citing works
“It is also known that mutations of proteins involved in mitochondrial turnover promote diabetic neurological diseases [86].”
BackgroundAutophagy in the eye: from physiology to pathophysiology
Liton, P. B., Boesze‐Battaglia, K., Boulton, M. E., Boya, P., Ferguson, T. A., Ganley, I. G., Kauppinen, A., Laurie, G. W., Mizushima, N., Morishita, H., et al. (2023) · Autophagy Reports · doi:10.1080/27694127.2023.2178996 · Cited by 29 · see citing works
Liu, M., Wang, Q., Wu, W., Chen, M., Zhang, P., Guo, M., Lin, H., Ma, Z., Zhou, H., & Fan, H. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010912 · Cited by 28 · see citing works
ROCK2 inhibition: A futuristic approach for the management of Alzheimer’s disease
Mani, S., Jindal, D., Chopra, H., Jha, S. K., Singh, S. K., Ashraf, G. M., Kamal, M., Iqbal, D., Chellappan, D. K., Dey, A., et al. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104871 · Cited by 28 · see citing works
Evans, C. S., & Holzbaur, E. L. F. (2020) · Autophagy · doi:10.1080/15548627.2020.1734330 · Cited by 28 · see citing works
Self-citationA Healthy Heart and a Healthy Brain: Looking at Mitophagy
Luo, H., Zhang, R., Krigman, J., McAdams, A., Ozgen, S., & Sun, N. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00294 · Cited by 25 · see citing works
TSG101 negatively regulates mitochondrial biogenesis in axons
Lin, T.-H., Bis‐Brewer, D. M., Sheehan, A. E., Townsend, L., Maddison, D. C., Zuchner, S. L., Smith, G. A., & Freeman, M. R. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2018770118 · Cited by 26 · see citing works
Advances in SIRT3 involvement in regulating autophagy-related mechanisms
Xi, S., Chen, W., & Ke, Y. (2024) · Cell Division · doi:10.1186/s13008-024-00124-y · Cited by 25 · see citing works
“Mitochondrial autophagy is considered a bona fide strategy to limit mitochondrial ROS production by specifically isolating and phagocytosing aged and damaged mitochondria in lysosomes [87].”
BackgroundEndo-IP and lyso-IP toolkit for endolysosomal profiling of human-induced neurons
Hundley, F. V., Gonzalez‐Lozano, M. A., Gottschalk, L. M., Cook, A. N. K., Zhang, J., Paulo, J. A., & Harper, J. W. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2419079121 · Cited by 24 · see citing works
“…with unique properties ( 35 , 44 – 46 ). iNeurons maintain many features of animal - derived neurons, including intact axonal and dendritic trafficking pathways, and reliance on organelle quality control systems such as autophagy to remove damaged or superfluous organelles ( 16 , 47 , 48 ).”
Juncker, M. A., Kim, C., Reed, R. E., Haas, A. L., Schwartzenburg, J., & Desai, S. D. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166102 · Cited by 24 · see citing works
Candelise, N., Salvatori, I., Scaricamazza, S., Nesci, V., Zenuni, H., Ferri, A., & Valle, C. (2022) · Metabolites · doi:10.3390/metabo12030233 · Cited by 25 · see citing works
“The ALS-linked mutation OPTNE478G was demonstrated to be sufficient to disrupt mitophagy and to cause neurodegeneration in primary neurons [65].”
BackgroundProspects for gene replacement therapies in amyotrophic lateral sclerosis
Giovannelli, I., Higginbottom, A., Kirby, J., Azzouz, M., & Shaw, P. J. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00751-5 · Cited by 23 · see citing works
Gene therapy breakthroughs in ALS: a beacon of hope for 20% of ALS patients
Xie, Q., Li, K., Chen, Y., Li, Y., Jiang, W., Cao, W., Yu, H., Fan, D., & Deng, B. (2025) · Translational Neurodegeneration · doi:10.1186/s40035-025-00477-6 · Cited by 22 · see citing works
“OPTN, as a selective autophagy receptor, identifies and binds ubiquitinated proteins and damaged organelles such as mitochondria, transporting them to autophago-somes for degradation [156].”
Peripheral neuropathy in mitochondrial disease
Horváth, R., Medina, J. M., Reilly, M. M., Shy, M. E., & Zuchner, S. L. (2023) · Handbook of clinical neurology · doi:10.1016/b978-0-12-821751-1.00014-2 · Cited by 22 · see citing works
PINK1 regulated mitophagy is evident in skeletal muscles
Singh, F., Wilhelm, L. P., Prescott, A. R., Ostacolo, K., Zhao, J., Ogmundsdottir, M. H., & Ganley, I. G. (2024) · Autophagy Reports · doi:10.1080/27694127.2024.2326402 · Cited by 21 · see citing works
Mitochondrial damage triggers the concerted degradation of negative regulators of neuronal autophagy
Basak, B., & Holzbaur, E. L. F. (2025) · Nature Communications · doi:10.1038/s41467-025-62379-5 · Cited by 20 · see citing works
“Previous work from our lab has shown that fusion of mitopha-gosomes with lysosomes is slow, and in fact is the rate-limiting step in neuronal mitophagy 36 .”
Self-citationVevea, J., & Chapman, E. R. (2023) · Journal of Neuroscience · doi:10.1523/jneurosci.1356-22.2023 · Cited by 20 · see citing works
“Low doses of AA ( , 10 n M ) increased retrograde mitochondrial transport (M. Y. Lin et al., 2017) or had no effect on motility but induced mitophagy in the soma (Evans and Holzbaur, 2020).”
Stavropoulos, F., Sargiannidou, I., Potamiti, L., Kagiava, A., Panayiotidis, M. I., Bae, J. H., Yeom, S. C., Lee, J. Y., & Kleopa, K. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111569 · Cited by 21 · see citing works
“Moreover, mitophagy is a much slower process in neurons compared to non-neuronal cells [43,44], and this may be another factor rendering peripheral nerves more susceptible to MFN2 mutations, as their greater axonal length seems to be a rate-limiting factor for mitophagy.”
BackgroundMitophagy mechanisms in neuronal physiology and pathology during ageing
Markaki, M., Tsagkari, D., & Tavernarakis, N. (2021) · Biophysical Reviews · doi:10.1007/s12551-021-00894-7 · Cited by 18 · see citing works
“Specifically, autophagosome fusion with lysosome and acidification occur hours after the stimulus of mitophagy has emerged (Evans and Holzbaur 2020b).”
BackgroundHuang, K.-C., Gomes, C., Shiga, Y., Belforte, N., VanderWall, K. B., Lavekar, S. S., Fligor, C. M., Harkin, J., Hetzer, S. M., Patil, S., et al. (2024) · Acta Neuropathologica Communications · doi:10.1186/s40478-024-01872-2 · Cited by 18 · see citing works
“During the process of autophagy, OPTN is necessary to recruit the microtubule-associated protein light chain 3 (LC3) for the engulfment of protein aggregates and/ or damaged organelles by formation of the autophago-some [29, 43].”
BackgroundLi, D., Geng, D., & Wang, M. (2024) · The FASEB Journal · doi:10.1096/fj.202401409r · Cited by 17 · see citing works
“192 ,193”
The compartmentalised nature of neuronal mitophagy: molecular insights and implications
Borbolis, F., & Palikaras, K. (2022) · Expert Reviews in Molecular Medicine · doi:10.1017/erm.2022.31 · Cited by 16 · see citing works
“142).”
Defective PTEN-induced kinase 1/Parkin mediated mitophagy and neurodegenerative diseases
Braun, M. M., & Puglielli, L. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.1031153 · Cited by 16 · see citing works
“However, it is unclear if this increase results in increased degradation of mitochondria since TDP-43 expression also increases the percentage of stationary mitochondria in axons and neurites (Cai et al., 2012; Wang et al., 2013; Evans and Holzbaur, 2020a).”
BackgroundMethodInfluentialHuynh, D. T., Tsolova, K. N., Watson, A. J., Khal, S. K., Green, J. R., Li, D., Hu, J., Soderblom, E. J., Chi, J., Evans, C. S., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-42227-0 · Cited by 15 · see citing works
“Therefore, we used live-cell fl uorescence microscopy 75 to test whether NF-L O-GlcNAcylation impacts organelle motility.”
Self-citationAltered Mitochondrial Protein Homeostasis and Proteinopathies
Jishi, A., & Qi, X. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.867935 · Cited by 15 · see citing works
“Mitochondria are engulfed in mitophagosomes and degraded, though the process of their degradation is rather inefficient due to the slow acidification of these structures (Liu et al., 2018; Evans and Holzbaur, 2020).”
BackgroundOptineurin Deficiency and Insufficiency Lead to Higher Microglial TDP-43 Protein Levels
Prtenjača, N., Rob, M., Alam, M. S., Markovinović, A., Stuani, C., Buratti, E., & Munitić, I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23126829 · Cited by 14 · see citing works
“Notably, the majority of results on the mechanistic link between optineurin and autophagy were obtained on immortalized cell lines rather than the relevant CNS cells [28,29,35], and few recent studies have been performed in neurons or neuronal cell lines [33,36].”
BackgroundWen, D., Ji, Y., Li, Y., Duan, W., Wang, Y., Li, Z., Tao, M., & Liu, Y. (2023) · FEBS Journal · doi:10.1111/febs.17009 · Cited by 14 · see citing works
“These organelles carry out cellular functions, including Ca 2 + buffering and energy generation, via the MMP. Mitochondrial depolarization or damage impairs cell function and results in the transmission of signals to maintenance pathways to repair or eliminate dysfunctional organelles [35].”
BackgroundLi, Y., Li, Z., Grillo, E., Desler, C., Navarro, C., Bohr, V. A., Berliocchi, L., & Rasmussen, L. J. (2024) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2024.07.013 · Cited by 14 · see citing works
Jeong, Y., Davis, C.-H. O., Muscarella, A. M., Navarro, H. H., Deshpande, V. A., Moore, L. G., Keun-young Kim, A., Ellisman, M. H., & Marsh‐Armstrong, N. (2025) · eLife · doi:10.7554/elife.103844 · Cited by 12 · see citing works
“…( Xie and Klionsky, 2007 ; Mizushima and Komatsu, 2011 ; Fu et al., 2014 ; Wong and Holzbaur, 2014b ; Tammineni et al., 2017 ; Stavoe et al., 2019 ; Evans and Holzbaur, 2020 ; Boecker et al., 2021 ; Kuijpers et al., 2021 ), we used the EGFP-LC3b signal to create a mask to demark the RGC axons, so…”
InfluentialYi, S., Zheng, Y., Yi, Z., Wang, Y., Jiang, Y., Ouyang, J., Li, S., Xiao, X., Sun, W., Wang, P., et al. (2023) · Genes · doi:10.3390/genes14040952 · Cited by 12 · see citing works
“As a multifactorial mitochondrial disorder, it is assumed to be affected by poor maternal nutrition or hazardous exposure prior to and during pregnancy, as the bio-energetically impaired mitochondria are likely present in the ovum and transmits to zygote, which act as an additive hit to the mitochondrial dysfunction c…”
BackgroundSung, H., & Lloyd, T. E. (2023) · Autophagy · doi:10.1080/15548627.2023.2249750 · Cited by 11 · see citing works
“The soma is thought to be the primary site of major degradative pathways and is enriched in acidified lysosomes [12–15], whereas presynaptic terminals, responsible for signal transmission, are the primary site of autophagy initiation and autophagosome formation [9,16–18].”
BackgroundDrosophila Primary Neuronal Cultures as a Useful Cellular Model to Study and Image Axonal Transport
Voelzmann, A., & Sánchez‐Soriano, N. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-1990-2_23 · Cited by 11 · see citing works
Enhancing CNS mitophagy: drug development and disease-relevant models
Dhar, K. S., Townsend, B., Montgomery, A. P., Danon, J. J., Pagan, J. K., & Kassiou, M. (2024) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2024.09.002 · Cited by 10 · see citing works
Mitochondrial motility modulators coordinate quality control dynamics to promote neuronal health
Jenkins, J. E., Fazli, M., & Evans, C. S. (2024) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2024.102383 · Cited by 9 · see citing works
Self-citationChen, K., Padilla, C. G., Kiselyov, K. I., & Kozai, T. D. Y. (2023) · Biomaterials · doi:10.1016/j.biomaterials.2023.122316 · Cited by 9 · see citing works
Lu, Y., Yang, Q., Yang, S., Zhang, J., Zhang, Y., Lu, J., Li, Z., Shen, Y., Yan, W., Jiang, Q., et al. (2025) · Nano Research · doi:10.26599/nr.2025.94907463 · Cited by 8 · see citing works
Li, W., Shao, G., & Qi, R. (2025) · Cell Regeneration · doi:10.1186/s13619-025-00268-4 · Cited by 9 · see citing works
“Mitochondria are central to cellular energy production via oxidative phosphorylation and the regulation of intra-cellular signaling cascades (Evans and Holzbaur 2020).”
ALS-Linked VapB P56S Mutation Alters Neuronal Mitochondrial Turnover at the Synapse
Wong, H.-T., Lang, A. E., Stein, C., & Drerup, C. M. (2024) · Journal of Neuroscience · doi:10.1523/jneurosci.0879-24.2024 · Cited by 8 · see citing works
Presynapses are mitophagy pit stops that prevent axon degenerationPreprint
Lam, W. K., Lindblom, R. S. J., Milky, B., Mazzachi, P., Hadian-Jazi, M., Küng, C. J., Khuu, G., Uoselis, L., Nguyen, T. N., Skulsuppaisarn, M., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.09.611943 · Cited by 9 · see citing works
Morphological multiparameter filtration and persistent homology in mitochondrial image analysis
Chung, Y.-M., Hu, C.-S., Sun, E., & Tseng, H. C. (2024) · PLoS ONE · doi:10.1371/journal.pone.0310157 · Cited by 7 · see citing works
Guo, Y., Xia, P., Tian, Y., Fu, D., Hu, X., Xie, K., Dong, W., Zhang, W., Liu, D., Shen, R., et al. (2025) · Cell Death Discovery · doi:10.1038/s41420-025-02641-3 · Cited by 7 · see citing works
Chun, C., Lee, J. H., Bothwell, M. A., Nghiem, P., Smith, A. S. T., & Mack, D. L. (2024) · Journal of Neuroscience · doi:10.1523/jneurosci.1787-23.2024 · Cited by 7 · see citing works
Probing β-Cell Biology in Space and Time
Drigo, R. A. E. (2021) · Diabetes · doi:10.2337/dbi21-0008 · Cited by 6 · see citing works
“Age mosaicism has recently been observed in the vastly different lifetimes of biological elements and systems, from the varying half-lives of NAD(1) across tissues (79) to the long-term association of transcription factors with the chromatin to determine cell phenotype (80), to the longevity of NPCs, histones, and mit…”
BackgroundRadiation and Diabetic Retinopathy: A Dark Synergy
Gardiner, T. A., ARCHER, D. B., Silvestri, G., & Amoaku, W. M. K. (2023) · International Journal of Translational Medicine · doi:10.3390/ijtm3010011 · Cited by 6 · see citing works
Liu, Y., Li, J., Xiong, Y., Tan, C., Li, C., Cao, Y., Xie, W., & Deng, Z. (2024) · Scientific Reports · doi:10.1038/s41598-024-62748-y · Cited by 6 · see citing works
The Unified Theory of Neurodegeneration Pathogenesis Based on Axon Deamidation
Joseph, D. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26094143 · Cited by 6 · see citing works
“Regarding oxidative stress, Evans et al. [134] reported that oxidative stress renders mitophagy unable to maintain the health of the neuron, leading to neurodegeneration.”
Correcting abnormal mitochondrial dynamics to facilitate tumor treatment
Yang, B., Lin, Y., & Shen, Y. (2023) · Mitochondrial Communications · doi:10.1016/j.mitoco.2023.07.001 · Cited by 6 · see citing works
Sun, L., 宁波大学农产品质量安全危害因子与风险防控国家重点实验室, 浙. 宁. 3., Dai, Y.-F., You, M.-X., Li, C., & 青岛海洋科学与技术国家实验室海洋渔业科学与食物产出过程功能实验室, 山. 青. 2. (2023) · 动物学研究 · doi:10.24272/j.issn.2095-8137.2023.106 · Cited by 6 · see citing works
Molecular aspects of cytoprotection by Optineurin during stress and disease
Swarup, G., Medchalmi, S., Ramachandran, G., & Sayyad, Z. (2025) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2024.119895 · Cited by 5 · see citing works
Li, Z., Liu, J., Ju, J., Peng, X., Zhao, W., Ren, J., Jia, X., Wang, J., Tu, Y., & Gao, F. (2025) · British Journal of Pharmacology · doi:10.1111/bph.70048 · Cited by 5 · see citing works
“Damaged mitochondria are trafficked back to the soma (retrograde) for degradation, avoiding the local accumulation of these damaged mitochondria (Evans & Holzbaur, 2020).”
Li, N., Hou, H., Su, D., Yang, B., Ni, R., Ma, G., Sun, S., Ma, Q., Peng, Q., Chen, S., et al. (2025) · Autophagy · doi:10.1080/15548627.2025.2572528 · Cited by 5 · see citing works
“During PINK1-PRKN-mediated mitophagy, LC3B is recruited to damaged mitochondria after the mitochondrial translocation of the E3 ubiquitin ligase PRKN and mitophagy receptor OPTN [31].”
Pabon, A., Bhupana, J. N., & Wong, C. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-23-02095 · Cited by 6 · see citing works
“Damaged distal mitochondria are transported to neuronal soma for mitophagy (Zheng et al., 2019; Evans and Holzbaur, 2020).”
BackgroundGuttipatti, P., Saadallah, N., Ji, R., Avula, U. M. R., Goulbourne, C. N., & Wan, E. Y. (2024) · Journal of Structural Biology · doi:10.1016/j.jsb.2024.108110 · Cited by 5 · see citing works
- Authors
- Evans, C. S., & Holzbaur, E. L.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Holzbaur, Erika LF
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2020-01-14
- Volume
- 9
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC6959996
- OpenAlex
- W2999206621
- Cited by
- 137
- References
- 113
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 26 · 2023: 20 · 2022: 26 · 2021: 25 · 2020: 7
- FWCI
- 13.99
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Neurological Disorders and Stroke (R37 NS060698)
- Howard Hughes Medical Institute (Hanna H Gray Fellowship)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- mitophagy, optineurin, mitochondrial degradation, lysosome fusion, lysosomal acidification, oxidative stress, mitochondrial depolarization, amyotrophic lateral sclerosis, neuronal health, neurodegeneration, hippocampal neurons, age-related decline
- MeSH terms
- Autophagosomes, Animals, Autophagy, Axons, HeLa Cells, Hippocampus, Humans, Kinetics, Lysosomes, Mitochondria, Mutation, Neurons, Phagosomes, Protein Kinases, Rats, Sprague-Dawley, Reactive Oxygen Species, Oxidative Stress, Neurodegenerative Diseases, RNA, Small Interfering, Transcription Factor TFIIIA, Rats, Membrane Potential, Mitochondrial, Mitophagy
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