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Cited by 205Autophagy in Disease and TherapyUbiquitin and proteasome pathwaysParkinson's Disease Mechanisms and Treatments

Critical role of mitochondrial ubiquitination and the OPTN–ATG9A axis in mitophagy

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Yamano, Koji, Kikuchi, Reika, Kojima, Waka, Hayashida, Ryota, Koyano, Fumika, Kawawaki, Junko, Shoda, Takuji, Demizu, Yosuke +3 more·2020·Journal of Cell Biology
DOI 10.1083/jcb.201912144PMC PMC7480101
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Abstract

Damaged mitochondria are selectively eliminated in a process called mitophagy. Parkin and PINK1, proteins mutated in Parkinson’s disease, amplify ubiquitin signals on damaged mitochondria with the subsequent activation of autophagic machinery. Autophagy adaptors are thought to link ubiquitinated mitochondria and autophagy through ATG8 protein binding. Here, we establish methods for inducing mitophagy by mitochondria-targeted ubiquitin chains and chemical-induced mitochondrial ubiquitination. Using these tools, we reveal that the ubiquitin signal is sufficient for mitophagy and that PINK1 and Parkin are unnecessary for autophagy activation per se. Furthermore, using phase-separated fluorescent foci, we show that the critical autophagy adaptor OPTN forms a complex with ATG9A vesicles. Disruption of OPTN–ATG9A interactions does not induce mitophagy. Therefore, in addition to binding ATG8 proteins, the critical autophagy adaptors also bind the autophagy core units that contribute to the formation of multivalent interactions in the de novo synthesis of autophagosomal membranes near ubiquitinated mitochondria.

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  • ATG9A has been linked to OPTN, which plays an important role as an adapter for PINK1-PRKN mitophagy.

    “has been linked to OPTN, which plays an important role as an adapter for PINK1-PRKN mitophagy [12, 34, 35].”

    From miRNA family miR-29 inhibits PINK1-PRKN signaling via ATG9A (2026) · cites this paper as [34]

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Cited by

Sorted by citations

Authors
Yamano, K., Kikuchi, R., Kojima, W., Hayashida, R., Koyano, F., Kawawaki, J., Shoda, T., Demizu, Y., Naito, M., Tanaka, K., & Matsuda, N.
Affiliations
  • Tokyo Metropolitan Institute of Medical Science (JP)
  • National Institute of Health Sciences (JP)
Corresponding author
Yamano, Koji
ORCID
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2020-06-17
Volume
219
Issue
9
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.201912144
PMC
PMC7480101
OpenAlex
W3036585903
Cited by
205
References
11
Citations by year
2026: 26 · 2025: 44 · 2024: 33 · 2023: 33 · 2022: 30 · 2021: 33 · 2020: 6
FWCI
18.27
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Cell Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Japan Society for the Promotion of Science (JP18H05500, JP18K06237, JP17J03737, JP18K14708, JP18H02443, JP19H05712, JP19H00997, JP17K08385, JP18H05502, JP16H05090)
  • Chieko Iwanaga Fund for Parkinson's Disease Research
  • Takeda Science Foundation
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords
mitophagy, mitochondrial ubiquitination, optineurin, ATG9A, PINK1, Parkin, autophagy adaptors, ATG8, Parkinson's disease, ubiquitin chains
MeSH terms
Autophagy-Related Proteins, Animals, Autophagy, Carrier Proteins, Cells, Cultured, HeLa Cells, Humans, Mammals, Membrane Proteins, Mitochondria, Protein Kinases, Cell Cycle Proteins, Ubiquitin, Membrane Transport Proteins, Vesicular Transport Proteins, Ubiquitin-Protein Ligases, HCT116 Cells, Cell Line, Tumor, Ubiquitination, HEK293 Cells, Mitophagy

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