TBK1 is ubiquitinated by TRIM5α to assemble mitophagy machinery
Permanent lenke
https://hdl.handle.net/10037/34993Dato
2024-05-29Type
Journal articleTidsskriftartikkel
Peer reviewed
Forfatter
Saha, Bhaskar; Olsvik, Hallvard Lauritz; Williams, Geneva L.; Oh, Seeun; Evjen, Gry; Sjøttem, Eva Synnøve; Mandell, Michael A.Sammendrag
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 TRIM5a and is required for TBK1 to interact
with and activate a set of ubiquitin-binding autophagy adaptors including NDP52, p62/SQSTM1, and NBR1.
Autophagy adaptors, along with TRIM27, enable TRIM5a to engage with TBK1 following mitochondrial damage. TRIM5a’s ubiquitin ligase activity is required for the accumulation of active TBK1 on damaged mitochondria in Parkin-dependent and Parkin-independent mitophagy pathways. Our data support a model in which
TRIM5a provides a mitochondria-localized, ubiquitin-based, self-amplifying assembly platform for TBK1 and
mitophagy adaptors that is ultimately necessary for the recruitment of the core autophagy machinery.
Forlag
ElsevierSitering
Saha, Olsvik, Williams, Oh, Evjen, Sjøttem, Mandell. TBK1 is ubiquitinated by TRIM5α to assemble mitophagy machinery. Cell reports. 2024;43(6)Metadata
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Copyright 2024 The Author(s)