The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
TBK1 controls autophagosomal engulfment of polyubiquitinated mitochondria through p62/SQSTM1 phosphorylation
Abstract
Selective autophagy adaptor proteins, including p62/SQSTM1, play pivotal roles in the targeted degradation of ubiquitinated proteins or organelles through the autophagy-lysosome system. However, how autophagy adaptors promote the autophagosomal engulfment of selected substrates is poorly understood. Here, we show that p62 phosphorylation at S403 is required for the efficient autophagosomal engulfment of polyubiquitinated mitochondria during Parkin-dependent mitophagy. p62 is able to interact with Parkin-recruited mitochondria without S403 phosphorylation under mitophagy-inducing conditions, but those mitochondria are not enclosed by autophagosomes. Intriguingly, the S403 phosphorylation occurs only in the early period of mitochondrial depolarization. Optineurin and TANK-binding kinase 1 (TBK1) are transiently recruited to the polyubiquitinated mitochondria, and the activated TBK1 phosphorylates p62 at S403. TBK1 inhibitor, BX795, prevents the p62-mediated autophagosomal engulfment of Parkin-recruited mitochondria. Our results suggest that TBK1-mediated S403 phosphorylation regulates the efficient autophagosomal engulfment of ubiquitinated mitochondria as an immediate response to the mitochondrial depolarization.
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In the citing paper
“Additionally, TBK1 amplifies the signaling cascade for mitophagy by phosphorylating OPTN and SQSTM1 (which enhances binding to ubiquitin and LC3) and promoting TBK1 autophosphorylation in a positive-feedback manner [58,59].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [59]
In the citing paper
“Through its phosphorylation of the autophagy receptors OPTN, SQSTM1, and CALCOCO2/NDP52 (calcium binding and coiled-coil domain 2) [58,59,194], TBK1 regulates several aspects of autophagy, including macroautophagy, xenophagy and mitophagy [59,90,148,194–196].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [59]
In the citing paper
“Mitochondrial protein ubiquitination promotes mitochondrial recruitment of autophagy regulators and receptors such as TBK1 and optineurin (Heo et al., 2015, Matsumoto et al., 2015, Richter et al., 2016).”
From A Cell-Based High-Throughput Screening Identified Two Compounds that Enhance PINK1-Parkin Signaling (2020) · cites this paper as Matsumoto et al., 2015
Citations
Cites
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Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
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PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1
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Self-citationSelective autophagy mediated by autophagic adapter proteins
Johansen, T., & Lamark, T. (2011) · Autophagy · doi:10.4161/auto.7.3.14487 · Cited by 1,788
Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin
Tanaka, A., Cleland, M. M., Xu, S., Narendra, D. P., Suen, D.-F., Karbowski, M., & Youle, R. J. (2010) · Journal of Cell Biology · doi:10.1083/jcb.201007013 · Cited by 1,369
Phosphorylation of the Autophagy Receptor Optineurin Restricts Salmonella 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
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Mechanism and medical implications of mammalian autophagy
Dikic, I., & Elazar, Z. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0003-4 · Cited by 2,771
Hardiman, O. M., Al‐Chalabi, A., Chiò, A., Corr, E. M., Logroscino, G., Robberecht, W., Shaw, P. J., Simmons, Z., & van den Berg, L. H. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.71 · Cited by 2,237
Mitophagy and Quality Control Mechanisms in Mitochondrial Maintenance
Pickles, S., Vigié, P., & Youle, R. J. (2018) · Current Biology · doi:10.1016/j.cub.2018.01.004 · Cited by 2,081
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 1,088
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
Metadata
- Authors
- Matsumoto, G., Shimogori, T., Hattori, N., & Nukina, N.
- Affiliations
- RIKEN Center for Brain Science (JP)
- Juntendo University (JP)
- Corresponding author
- Matsumoto, Gen
- Nukina, Nobuyuki
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-05-13
- Volume
- 24
- Issue
- 15
- Pages
- 4429-4442
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2167192779
- Cited by
- 317
- References
- 45
- Citations by year
- 2026: 19 · 2025: 25 · 2024: 21 · 2023: 35 · 2022: 31 · 2021: 31 · 2020: 38 · 2019: 28 · 2018: 39 · 2017: 27 · 2016: 19 · 2015: 4
- FWCI
- 23.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- TBK1, p62, mitophagy, Parkin, optineurin, mitochondrial depolarization, selective autophagy, BX795, autophagy-lysosome system
- MeSH terms
- Sequestosome-1 Protein, Animals, Autophagy, Cell Line, Humans, Mitochondria, Phosphorylation, Protein Serine-Threonine Kinases, Mice, Knockout, Polyubiquitin, Ubiquitin-Protein Ligases, Adaptor Proteins, Signal Transducing, Mice, Mitophagy
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