Evidence map›Paper›PMID 37905089›Full record

ArticlebioRxiv : the preprint server for biology2023

TBK1 is ubiquitinated by TRIM5α to assemble mitophagy machinery.

Bhaskar Saha, Hallvard Olsvik, Geneva L Williams, Seeun Oh, Gry Evjen, Eva Sjøttem, Michael A Mandell

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Bhaskar SahaDepartment of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 USA.
Hallvard OlsvikAutophagy Research Group, Department of Medical Biology, University of Tromsø-The Arctic University of Norway, Tromsø, Norway.
Geneva L WilliamsBiomedical Sciences Graduate Program, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 USA.
Seeun OhDepartment of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 USA.
Gry EvjenAutophagy Research Group, Department of Medical Biology, University of Tromsø-The Arctic University of Norway, Tromsø, Norway.
Eva SjøttemAutophagy Research Group, Department of Medical Biology, University of Tromsø-The Arctic University of Norway, Tromsø, Norway.
Michael A MandellDepartment of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 USA.
University of New Mexico · USUiT The Arctic University of Norway · NO

Funding

Unfolded Protein Response and Autophagy in T Helper Cell Effector FunctionP20GM121176 · NIGMS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Monica Rosas Lemus · 2017 to 2026
$24.9M
Cellular responses to retroviral capsid recognitionR01AI155746 · NIAID · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI MANDELL, MICHAEL AARON · 2021 to 2025
$2.1M
NIAID NIH HHS R01 AI155746NIGMS NIH HHS P20 GM121176
6 · The paper itself

Abstract

Ubiquitination of mitochondrial proteins provides a basis for the downstream recruitment of mitophagy machinery, yet whether ubiquitination of the machinery itself contributes to mitophagy is unknown. Here, we show that K63-linked polyubiquitination of the key mitophagy regulator TBK1 is essential for its mitophagy functions. This modification is catalyzed by the ubiquitin ligase TRIM5α. Mitochondrial damage triggers TRIM5α's auto-ubiquitination and its interaction with ubiquitin-binding autophagy adaptors including NDP52, optineurin, and NBR1. Autophagy adaptors, along with TRIM27, enable TRIM5α to engage with TBK1. TRIM5α with intact ubiquitination function is required for the proper accumulation of active TBK1 on damaged mitochondria in Parkin-dependent and Parkin-independent mitophagy pathways. Additionally, we show that TRIM5α can directly recruit autophagy initiation machinery to damaged mitochondria. Our data support a model in which TRIM5α provides a self-amplifying, mitochondria-localized, ubiquitin-based, assembly platform for TBK1 and mitophagy adaptors that is ultimately required to recruit the core autophagy machinery.

Indexed as

autophagyLC3 interacting (LIR) motifNBR1NDP52Optineurinp62TAX1BP1TBK1TRIM27/RFPTRIM5αTripartite-motifubiquitin ligase

Identifiers

PMID37905089
PMCPMC10614974
OpenAlexW4387822107

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.