The DOI matches its Crossref record; 112 of the 113 references it cites were found in a registry or an index.
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 [259]”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [259]
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1 retracted
RETRACTED ARTICLE: Parkin and PINK1 mitigate STING-induced inflammation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×
“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×
“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
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×
“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×
“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 PINK1
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×
“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
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×
“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
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×
“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).”
BackgroundInfluential
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Items 101–137 of 137
Optineurin Dysfunction in Amyotrophic Lateral Sclerosis: Why So Puzzling?
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“, 2016) and in in vitro neuronal cultures (Evans and Holzbaur, 2020).”
BackgroundNon-canonical roles of lysosomes in neurons
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“On the contrary, given that the rates of autophagic organelle biogenesis and turnover are different in distinct cell types (Evans and Holzbaur, 2020; David et al., 2021; Klionsky et al. 2021), it highlights the need for future studies to define which WASP-family members are the most relevant in…”
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Self-citationEffects of Parkin on the Mitochondrial Genome in the Heart and Brain of Mitochondrial Mutator Mice
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PINK1/Parkin-dependent mitophagy mediates astrocytic inflammatory responses to mitochondrial damagePreprint
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Self-citationFazli, M., & Evans, C. S. (2023) · Journal of Visualized Experiments · doi:10.3791/65304 · Cited by 1
Self-citationPowering Up the Brain: Intercellular Mitochondrial Quality Control and Its Implication in Stroke
Zhou, X., Wu, S., Huang, T., Li, Y., Yang, J., Gu, Z., & Zhang, X. (2025) · Current Neuropharmacology · doi:10.2174/011570159x388351250620065716 · Cited by 1
“This distribution is particularly pronounced in regions with high ATP demands, such as presynaptic and postsynaptic terminals, active growth cones, axonal branches, and nodes of Ranvier [14].”
Turnover and Quality Control of Mitochondrial DNA
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Impairment of autophagy-lysosomal activity near the chronically implanted microelectrodesPreprint
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BackgroundInfluentialLocal ROS and inefficient autophagosome formation limit Optineurin-mediated mitophagy in neuronsPreprint
Green, J. R., Ojo, A. E., Gooden, M. K., Papell, L. D., Kalejaiye, T. D., & Evans, C. S. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.16.700014 · Cited by 1
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Vevea, J., & Chapman, E. R. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.07.06.499030
“Low doses of AA ( 10 nM) increased retrograde mitochondrial transport (M. Y. Lin et al., 2017), or had no effect on motility but induced mitophagy in the soma (Evans & Holzbaur, 2020).”
BackgroundUnraveling Pathophysiological Link Between Mitophagy Pathway and Vascular Dementia
Kumaş‐Kulualp, M., Kadırhan, Ö. A., & Demırci, M. (2022) · Archives of Neuroscience · doi:10.5812/ans-124588
“bates development of neurodegenerative diseases (40-42).”
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InfluentialSelf-citationMetabolite Regulation of Mitochondrial Quality Control and Regulated Cell Death
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Metadata
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Clinical 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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