Selective autophagy

Faruk, Mohammad Omar; Ichimura, Yoshinobu; Komatsu, Masaaki

doi:10.1111/cas.15112

Cited by 33 publications

(20 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This means that autophagy strictly regulates diverse biological phenomena through its selectivity as well as the ubiquitinproteasome system. 1,2 p62 was originally identified and termed sequestosome-1 (SQSTM1) by Shin due to its ability to form aggregates. 3 The SQSTM1 gene encoding p62/Sequestosome-1 (hereafter referred to as p62) is conserved in metazoans (a hybrid form of p62 and NBR1 exists in plants) and its expression is regulated by transcription factors such as NRF2, NF-κB, and MiT/TFE.…”

Section: Introductionmentioning

confidence: 99%

“…The latter is called selective autophagy and contributes to cellular homeostasis by degrading specific soluble proteins, supramolecular complexes, liquid–liquid phase‐separated droplets, abnormal or excess organelles, and pathogenic bacteria. This means that autophagy strictly regulates diverse biological phenomena through its selectivity as well as the ubiquitin–proteasome system 1,2 …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

p62 bodies: Phase separation, NRF2 activation, and selective autophagic degradation

Komatsu

2022

IUBMB Life

Self Cite

View full text Add to dashboard Cite

When p62/Sequestosome‐1 binds to a ubiquitinated protein, it undergoes liquid–liquid phase separation (LLPS) and forms a membraneless organelle, p62 body. There are two major physiological functions of the p62 body. One is effective autophagic degradation of ubiquitinated proteins and the other is antioxidant stress response, both of which contribute to cellular homeostasis. In this review, I review the history of p62 research in relation to autophagy and outline the formation, degradation, and physiological functions of the p62 body.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

p62 bodies: Phase separation, NRF2 activation, and selective autophagic degradation

Komatsu

2022

IUBMB Life

Self Cite

View full text Add to dashboard Cite

show abstract

“…Of the droplets that have a unique biological function and are degraded by autophagy, p62 bodies (also called p62 droplets) are liquid droplets formed by liquid-liquid phase separation (LLPS) of p62 and its binding partners, ubiquitinated proteins 4,5 . p62 bodies are involved in the regulation of intracellular proteostasis through their own autophagic degradation, and also contribute to the regulation of the major stress-response mechanism by sequestration of a client protein, kelch-like ECH-associated protein 1 (KEAP1) 6,7 .…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of phase-separated p62 bodies by ULK1 activates a redox-independent stress response

Ikeda

Noshiro

Morishita

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

NRF2 is a transcription factor responsible for antioxidant stress responses that is usually regulated in a redox-dependent manner. p62 bodies formed by liquid-liquid phase separation contain Ser349-phosphorylated p62, which participates in the redox-independent activation of NRF2. However, the regulatory mechanism and physiological significance of phosphorylation remain unclear. Herein, we identify ULK1 as a kinase responsible for phosphorylation of p62. ULK1 co-localizes with p62 bodies, and directly interacts with p62. This phosphorylation allows KEAP1 to be retained within p62 bodies, activating NRF2. p62S351E/+ mice are phosphomimetic knock-in mice in which Ser351 corresponding to human Ser349 is replaced by Glu. These mice, but not phosphodefective p62S351A/S351A mice, exhibit NRF2 hyperactivation and growth retardation, the latter caused by malnutrition and dehydration due to obstruction of the esophagus and forestomach secondary to hyperkeratosis. p62S351E/+ mice are a phenocopy of systemic Keap1-knockout mice. Our results expand our understanding of the physiological importance of the redox-independent NRF2 activation pathway and provide new insight into the role of phase separation in this process.

show abstract

“…A key early process in xenophagy is the ubiquitination (Ub) of target proteins (Alomairi et al, 2015;Dupont et al, 2010). Ub recruits autophagy receptor proteins to pathogens or target sites, including ruptured endosomal membranes (Alomairi et al, 2015;Kirkin et al, 2009;Faruk et al, 2021;Fujita et al, 2013). Autophagy receptor proteins include p62/sequestosome-1 (p62/SQSTM1) (hereafter designated p62), optineurin (OPTN), nuclear dot protein 52 (NDP52), Tax1-binding protein 1 (TAX1 BP1), a neighbor of the BRCA1 gene (NBR1), and NIX (BNIP3L).…”

Section: Introductionmentioning

confidence: 99%

TBK1 inhibitors enhance transfection efficiency by suppressing p62/SQSTM1 phosphorylation

et al. 2022

View full text Add to dashboard Cite

DNA transfection is an essential technique in the life sciences. Non-viral transfection reagents are widely used for transfection in basic science. However, low transfection efficiency is a problem in some cell types. This low efficiency can be primarily attributed to the intracellular degradation of transfected DNA by p62-dependent selective autophagy, specifically by p62 phosphorylated at the S403 residue (p62-S403-P). To achieve efficient DNA transfection, we focused on a phosphorylation process that generates p62-S403-P and investigated whether inhibition of this process affects transfection efficiency. One of the kinases that phosphorylate p62 is TBK1. The TBK1 gene depletion in murine embryonic fibroblast cells by genome editing caused a significant reduction or loss of p62-S405-P (equivalent to human S403-P) and enhanced transfection efficiency, suggesting that TBK1 is a major kinase that phosphorylates p62 at S403. Therefore, TBK1 is a viable target for drug treatment to increase transfection efficiency. Transfection efficiency was enhanced when cells were treated with one of the following TBK1 inhibitors BX795, MRT67307, or amlexanox. This effect was synergistically improved when the two inhibitors were used in combination. Our results indicate that TBK1 inhibitors enhanced transfection efficiency by suppressing p62 phosphorylation.

show abstract

Selective autophagy

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 33 publications

References 55 publications

p62 bodies: Phase separation, NRF2 activation, and selective autophagic degradation

p62 bodies: Phase separation, NRF2 activation, and selective autophagic degradation

Phosphorylation of phase-separated p62 bodies by ULK1 activates a redox-independent stress response

TBK1 inhibitors enhance transfection efficiency by suppressing p62/SQSTM1 phosphorylation

Contact Info

Product

Resources

About