K63-linked ubiquitylation induces global sequestration of mitochondria Article Swipe
Thibaud Richard
,
Laura K. Herzog
,
Julia Vornberger
,
Aldwin Suryo Rahmanto
,
Olle Sangfelt
,
Florian A. Salomons
,
Nico P. Dantuma
·
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1038/s41598-020-78845-7
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1038/s41598-020-78845-7
Even though K63-linked polyubiquitin chains do not target proteins for proteasomal degradation, they play nevertheless a complementary protective role in maintaining protein homeostasis by directing malfunctioning proteins and organelles to inclusion bodies or autophagosomes. A paradigm for this process is the sequestration and autophagic degradation of dysfunctional mitochondria. Although studies have shown that K63-ubiquitylation of mitochondrial proteins by the ubiquitin ligase Parkin is important in this process, it is presently not clear if this modification also suffices to initiate this cascade of events. To address this question, we have engineered the ubiquitin ligase ProxE3, which in an inducible manner synthesizes K63-linked ubiquitin chains on the surface of mitochondria. We found that the presence of K63-linked ubiquitin chains on mitochondria resulted in the recruitment of the ubiquitin adaptor p62 and induced a dramatic redistribution of mitochondria, which was reminiscent to the Parkin-facilitated sequestration in response to mitochondrial uncoupler. However, ProxE3 did not induce autophagic degradation of mitochondria. Our data show that K63-linked ubiquitin chains at the mitochondrial membrane are sufficient for the induction of mitochondrial sequestration, but not mitophagy, without the need of extrinsically inflicting mitochondrial dysfunction.
Related Topics
Concepts
Mitophagy
Parkin
Ubiquitin
Ubiquitin ligase
Mitochondrion
Cell biology
Autophagy
Signal transducing adaptor protein
Biology
Organelle
Protein degradation
Ubiquitin-Protein Ligases
Chemistry
Biochemistry
Signal transduction
Gene
Apoptosis
Parkinson's disease
Pathology
Disease
Medicine
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41598-020-78845-7
- https://www.nature.com/articles/s41598-020-78845-7.pdf
- OA Status
- gold
- Cited By
- 24
- References
- 36
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3118063230
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W3118063230Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1038/s41598-020-78845-7Digital Object Identifier
- Title
-
K63-linked ubiquitylation induces global sequestration of mitochondriaWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2020Year of publication
- Publication date
-
2020-12-18Full publication date if available
- Authors
-
Thibaud Richard, Laura K. Herzog, Julia Vornberger, Aldwin Suryo Rahmanto, Olle Sangfelt, Florian A. Salomons, Nico P. DantumaList of authors in order
- Landing page
-
https://doi.org/10.1038/s41598-020-78845-7Publisher landing page
- PDF URL
-
https://www.nature.com/articles/s41598-020-78845-7.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.nature.com/articles/s41598-020-78845-7.pdfDirect OA link when available
- Concepts
-
Mitophagy, Parkin, Ubiquitin, Ubiquitin ligase, Mitochondrion, Cell biology, Autophagy, Signal transducing adaptor protein, Biology, Organelle, Protein degradation, Ubiquitin-Protein Ligases, Chemistry, Biochemistry, Signal transduction, Gene, Apoptosis, Parkinson's disease, Pathology, Disease, MedicineTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
24Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 8, 2024: 6, 2023: 2, 2022: 5, 2021: 3Per-year citation counts (last 5 years)
- References (count)
-
36Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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