Shuffled ATG8 interacting motifs form an ancestral bridge between UFMylation and autophagy DOI Creative Commons
Lorenzo Picchianti, Víctor Sánchez de Medina Hernández, Ni Zhan

и другие.

The EMBO Journal, Год журнала: 2023, Номер 42(10)

Опубликована: Фев. 10, 2023

UFMylation involves the covalent modification of substrate proteins with UFM1 (Ubiquitin-fold modifier 1) and is important for maintaining ER homeostasis. Stalled translation triggers ER-bound ribosomes activates C53-mediated autophagy to clear toxic polypeptides. C53 contains noncanonical shuffled ATG8-interacting motifs (sAIMs) that are essential ATG8 interaction initiation. However, mechanistic basis sAIM-mediated remains unknown. Here, we show sAIMs conserved across eukaryotes but secondarily lost in fungi various algal lineages. Biochemical assays showed unicellular alga Chlamydomonas reinhardtii has a functional pathway, refuting assumption linked multicellularity. Comparative structural analyses revealed both bind C53, distinct way. Conversion into canonical AIMs impaired binding UFM1, while strengthening binding. Increased led autoactivation pathway sensitization Arabidopsis thaliana stress. Altogether, our findings reveal an ancestral role UFMylation-dependent fine-tuning activation.

Язык: Английский

Reshaping endoplasmic reticulum quality control through the unfolded protein response DOI Creative Commons
R. Luke Wiseman, Jaleh S. Mesgarzadeh, Linda M. Hendershot

и другие.

Molecular Cell, Год журнала: 2022, Номер 82(8), С. 1477 - 1491

Опубликована: Апрель 1, 2022

Язык: Английский

Процитировано

243

ER-Phagy: Quality Control and Turnover of Endoplasmic Reticulum DOI Creative Commons
Haruka Chino, Noboru Mizushima

Trends in Cell Biology, Год журнала: 2020, Номер 30(5), С. 384 - 398

Опубликована: Март 2, 2020

Язык: Английский

Процитировано

231

Crosstalk between ER stress, NLRP3 inflammasome, and inflammation DOI
Wei Li, Ting Cao,

Chunyi Luo

и другие.

Applied Microbiology and Biotechnology, Год журнала: 2020, Номер 104(14), С. 6129 - 6140

Опубликована: Май 24, 2020

Язык: Английский

Процитировано

225

A cross-kingdom conserved ER-phagy receptor maintains endoplasmic reticulum homeostasis during stress DOI Creative Commons
Madlen Stephani, Lorenzo Picchianti,

Alexander Gajic

и другие.

eLife, Год журнала: 2020, Номер 9

Опубликована: Авг. 27, 2020

Eukaryotes have evolved various quality control mechanisms to promote proteostasis in the endoplasmic reticulum (ER). Selective removal of certain ER domains via autophagy (termed as ER-phagy) has emerged a major mechanism. However, degree which ER-phagy is employed by other branches ER-quality remains largely elusive. Here, we identify cytosolic protein, C53, that specifically recruited autophagosomes during ER-stress, both plant and mammalian cells. C53 interacts with ATG8 distinct binding epitope, featuring shuffled interacting motif (sAIM). senses proteotoxic stress lumen forming tripartite receptor complex ER-associated ufmylation ligase UFL1 its membrane adaptor DDRGK1. The C53/UFL1/DDRGK1 activated stalled ribosomes induces degradation internal or passenger proteins ER. Consistently, mutants are highly susceptible stress. Thus, forms an ancient pathway bridges selective ribosome-associated

Язык: Английский

Процитировано

200

Proteolysis‐targeting chimeras in drug development: A safety perspective DOI Open Access
Kévin Moreau, Muireann Coen, Andrew X. Zhang

и другие.

British Journal of Pharmacology, Год журнала: 2020, Номер 177(8), С. 1709 - 1718

Опубликована: Фев. 5, 2020

Proteolysis‐targeting chimeras are a new drug modality that exploits the endogenous ubiquitin proteasome system to degrade protein of interest for therapeutic benefit. As first‐generation proteolysis‐targeting have now entered clinical trials oncology indications, it is timely consider theoretical safety risks inherent with this which include off‐target degradation, intracellular accumulation natural substrates E3 ligases used in system, saturation by ubiquitinated proteins, and liabilities associated “hook effect” This review describes vitro non‐clinical vivo data provide mechanistic insight these approaches being mitigate next generation chimera molecules extend applications beyond life‐threatening diseases.

Язык: Английский

Процитировано

167

The lysosome as an imperative regulator of autophagy and cell death DOI
Kewal Kumar Mahapatra, Soumya Ranjan Mishra, Bishnu Prasad Behera

и другие.

Cellular and Molecular Life Sciences, Год журнала: 2021, Номер 78(23), С. 7435 - 7449

Опубликована: Окт. 30, 2021

Язык: Английский

Процитировано

135

PPAR-γ signaling in nonalcoholic fatty liver disease: Pathogenesis and therapeutic targets DOI
Hao Chen, Huabing Tan, Juan Wan

и другие.

Pharmacology & Therapeutics, Год журнала: 2023, Номер 245, С. 108391 - 108391

Опубликована: Март 22, 2023

Язык: Английский

Процитировано

131

ER-Phagy, ER Homeostasis, and ER Quality Control: Implications for Disease DOI Creative Commons
Susan Ferro‐Novick, Fulvio Reggiori, Jeffrey L. Brodsky

и другие.

Trends in Biochemical Sciences, Год журнала: 2021, Номер 46(8), С. 630 - 639

Опубликована: Янв. 25, 2021

Язык: Английский

Процитировано

114

ER-phagy: mechanisms, regulation, and diseases connected to the lysosomal clearance of the endoplasmic reticulum DOI Creative Commons
Fulvio Reggiori, Maurizio Molinari

Physiological Reviews, Год журнала: 2022, Номер 102(3), С. 1393 - 1448

Опубликована: Фев. 21, 2022

ER-phagy (reticulophagy) defines the degradation of portions endoplasmic reticulum (ER) within lysosomes or vacuoles. It is part self-digestion (i.e., autophagic) programs recycling cytoplasmic material and organelles, which rapidly mobilize metabolites in cells confronted with nutrient shortage. Moreover, selective clearance ER subdomains participates control size activity during stress, reestablishment homeostasis after stress resolution, removal parts aberrant potentially cytotoxic has been segregated. relies on individual and/or concerted activation receptors, peripheral integral membrane proteins that share presence LC3/Atg8-binding motifs their cytosolic domains. involves physical separation from bulk network delivery to endolysosomal/vacuolar catabolic district. This last step accomplished by a variety mechanisms including macro-ER-phagy (in fragments are sequestered double-membrane autophagosomes eventually fuse lysosomes/vacuoles), micro-ER-phagy directly engulfed endosomes/lysosomes/vacuoles), direct fusion ER-derived vesicles lysosomes/vacuoles. dysfunctional specific human diseases, its regulators subverted pathogens, highlighting crucial role for cell organism life.

Язык: Английский

Процитировано

113

Principles of gene regulation quantitatively connect DNA to RNA and proteins in bacteria DOI
Rohan Balakrishnan, Matteo Mori, Igor Šegota

и другие.

Science, Год журнала: 2022, Номер 378(6624)

Опубликована: Дек. 8, 2022

Protein concentrations are set by a complex interplay between gene-specific regulatory processes and systemic factors, including cell volume shared gene expression machineries. Elucidating this is crucial for discerning designing systems. We quantitatively characterized factors that affect transcription translation genome-wide Escherichia coli across many conditions. The results revealed two design principles make regulation of insulated from machineries: RNA polymerase activity fine-tuned to match translational output, characteristics similar most messenger RNAs (mRNAs). Consequently, in bacteria, protein concentration primarily at the promoter level. A simple mathematical formula relates activities growth conditions, enabling quantitative inference omics data.

Язык: Английский

Процитировано

101