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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“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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Self-citationSelective autophagy mediated by autophagic adapter proteins
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Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin
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Phosphorylation of the Autophagy Receptor Optineurin Restricts Salmonella Growth
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Chemical N-degrons activate p62-mediated mitophagy to alleviate mitochondrial neuropathiesPreprint
Kwon, S. C., Kim, B.-S., Kim, H., Kang, D. E., Lee, G. E., Jung, E. J., Lee, M. J., Son, Y. S., Park, D.-H., Park, D. Y., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.19.706908
Khalil, B. (2016) · theses.fr (ABES) · doi:10.70675/4446111fz4182z4737zae76z7f117887a893
Étude de l'autophagie lors d'une co-infection par le virus de la rougeole et Salmonella typhimurium
Clavière, M. (2018) · theses.fr (ABES) · doi:10.70675/478193d3zdbefz4e9dzaf20z16e9b2167fe3
Novel FUS and CHCHD10 models to investigate pathogenic mechanisms in Amyotrophic Lateral Sclerosis
Bourefis, A.-R. (2019) · theses.fr (ABES) · doi:10.70675/45ab8515z9859z430fzb472z306dd61206c8
Biochemical characterization of mTORC1 regulation by glutamine metabolism
Bodineau, C. (2020) · theses.fr (ABES) · doi:10.70675/9d5aaabdz81bdz4118zb3edze237bdd8dee0
de Calbiac, H. (2019) · theses.fr (ABES) · doi:10.70675/bafe951fz8332z4b0azb55bzac8a4af1955b
Gautam, S., & Saran, S. (2026) · Microbiological Research · doi:10.1016/j.micres.2026.128564
Sun, N., Zhang, J., Xia, B., Yin, H., Xie, J., Liu, X., Li, M., Fang, L., Ji, G., Ma, G., et al. (2026) · PLoS Pathogens · doi:10.1371/journal.ppat.1014578
Dong, Y.-R., Wang, J.-R., Yang, Y., Cao, S.-P., Zhou, M.-C., Zeng, S.-X., Hui-qing, M., Wang, J., Zang, C., Li, F.-F., et al. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118503
Posttranslational Modifications of p62/SQSTM1 in Health and Disease
Wang, W., Jiang, X., Qiu, R., Wijaya, C. S., Chen, M., Wang, J., Zhu, L., Jin, H., & Feng, L. (2026) · MedComm · doi:10.1002/mco2.70949 · Cited by 1
Revisiting Inherited Metabolic Diseases ( IMDs ) Through the Lens of Selective Autophagy
Maddaluno, M., Cinque, L., Cetrangolo, V., & Leonibus, C. D. (2026) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.70259
EPG5 orchestrates iron compartmentalization through dual regulation in macroferritinophagy
Chen, Y., Yang, Y., Wang, R., Wang, H., 吴春燕, & Lu, Q. (2026) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2026.113646
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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