Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)¹

Autophagy, Journal Year: 2021, Volume and Issue: 17(1), P. 1 - 382

Published: Jan. 2, 2021

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered field. Our knowledge base relevant new technologies also been expanding. Thus, it is important to formulate on a regular basis updated monitoring autophagy different organisms. Despite numerous reviews, there continues be confusion regarding acceptable methods evaluate autophagy, especially multicellular eukaryotes. Here, present investigators select interpret examine related processes, reviewers provide realistic reasonable critiques reports that are focused these processes. These not meant dogmatic rules, because appropriateness any assay largely depends question being asked system used. Moreover, no individual perfect every situation, calling use multiple techniques properly monitor each experimental setting. Finally, several core components machinery implicated distinct autophagic processes (canonical noncanonical autophagy), implying genetic approaches block should rely targeting two or more autophagy-related genes ideally participate steps pathway. Along similar lines, proteins involved regulate other cellular pathways including apoptosis, all them can used as specific marker bona fide responses. critically discuss current assessing information they can, cannot, provide. ultimate goal encourage intellectual technical innovation

Language: Английский

---

TREM2 Is a Receptor for β-Amyloid that Mediates Microglial Function

Neuron, Journal Year: 2018, Volume and Issue: 97(5), P. 1023 - 1031.e7

Published: March 1, 2018

Language: Английский

---

The role of ubiquitination in tumorigenesis and targeted drug discovery

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Feb. 29, 2020

Ubiquitination, an important type of protein posttranslational modification (PTM), plays a crucial role in controlling substrate degradation and subsequently mediates the "quantity" "quality" various proteins, serving to ensure cell homeostasis guarantee life activities. The regulation ubiquitination is multifaceted works not only at transcriptional levels (phosphorylation, acetylation, methylation, etc.) but also level (activators or repressors). When regulatory mechanisms are aberrant, altered biological processes may induce serious human diseases, especially types cancer. In tumorigenesis, involve tumor metabolism, immunological microenvironment (TME), cancer stem (CSC) stemness so on. With regard some key proteins such as RagA, mTOR, PTEN, AKT, c-Myc P53 significantly regulates activity mTORC1, AMPK PTEN-AKT signaling pathways. addition, TLR, RLR STING-dependent pathways modulates TME. Moreover, core regulator triplets (Nanog, Oct4 Sox2) members Wnt Hippo-YAP participates maintenance CSC stemness. Based on components, including proteasome, E3 ligases, E1, E2 deubiquitinases (DUBs), many molecular targeted drugs have been developed combat Among them, small molecule inhibitors targeting bortezomib, carfilzomib, oprozomib ixazomib, achieved tangible success. MLN7243 MLN4924 (targeting E1 enzyme), Leucettamol A CC0651 nutlin MI-219 compounds G5 F6 DUB activity) shown potential preclinical treatment. this review, we summarize latest progress understanding substrates for their special functions metabolism regulation, TME modulation maintenance. therapeutic targets reviewed, effects drugs.

Language: Английский

---

Crosstalk Between Mammalian Autophagy and the Ubiquitin-Proteasome System

Frontiers in Cell and Developmental Biology, Journal Year: 2018, Volume and Issue: 6

Published: Oct. 2, 2018

Crosstalk Between Mammalian Autophagy and the Ubiquitin-Proteasome System Nur Mehpare Kocaturk1 Devrim Gozuacik1,2,3* 1Sabanci University, Faculty of Engineering Natural Sciences, Molecular Biology, Genetics Bioengineering Program, Istanbul, 34956, Turkey. 2Sabanci Center Excellence for Functional Surfaces Interfaces Nano Diagnostics (EFSUN), 3Sabanci University Nanotechnology Application (SUNUM), * Correspondence: Gozuacik [email protected] ubiquitin–proteasome system (UPS) are two major intracellular quality control recycling mechanisms that responsible cellular homeostasis in eukaryotes. Ubiquitylation is utilized as a degradation signal by both systems, yet, different play. The UPS short-lived proteins soluble misfolded whereas autophagy eliminates long-lived proteins, insoluble protein aggregates even whole organelles (e.g., mitochondria, peroxisomes) parasites bacteria). Both selective recognize their targets through ubiquitin tags. In addition to an indirect connection between systems ubiquitylated recent data indicate presence connections reciprocal regulation these pathways. this review, we summarize direct interactions crosstalks UPS, implications stress responses homeostasis.

Language: Английский

---

Quality control of the mitochondrion

Developmental Cell, Journal Year: 2021, Volume and Issue: 56(7), P. 881 - 905

Published: March 7, 2021

Language: Английский

---

The Eukaryotic Proteome Is Shaped by E3 Ubiquitin Ligases Targeting C-Terminal Degrons

Cell, Journal Year: 2018, Volume and Issue: 173(7), P. 1622 - 1635.e14

Published: May 17, 2018

Language: Английский

---

The emerging mechanisms and functions of microautophagy

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 24(3), P. 186 - 203

Published: Sept. 12, 2022

Language: Английский

---

The immunoproteasome and thymoproteasome: functions, evolution and human disease

Nature Immunology, Journal Year: 2018, Volume and Issue: 19(9), P. 923 - 931

Published: Aug. 7, 2018

Language: Английский

---

Dopamine, Oxidative Stress and Protein–Quinone Modifications in Parkinson's and Other Neurodegenerative Diseases

Angewandte Chemie International Edition, Journal Year: 2018, Volume and Issue: 58(20), P. 6512 - 6527

Published: Dec. 11, 2018

Abstract Dopamine (DA) is the most important catecholamine in brain, as it abundant and precursor of other neurotransmitters. Degeneration nigrostriatal neurons substantia nigra pars compacta Parkinson's disease represents best‐studied link between DA neurotransmission neuropathology. Catecholamines are reactive molecules that handled through complex control transport systems. Under normal conditions, small amounts cytosolic converted to neuromelanin a stepwise process involving melanization peptides proteins. However, excessive or extraneuronal can give rise nonselective protein modifications. These reactions involve oxidation quinone species depend on presence redox‐active transition metal ions such iron copper. Other oxidized metabolites likely participate post‐translational modification. Thus, protein–quinone modification heterogeneous multiple DA‐derived residues produce structural conformational changes proteins lead aggregation inactivation modified

Language: Английский

---

Selective Autophagy and Xenophagy in Infection and Disease

Frontiers in Cell and Developmental Biology, Journal Year: 2018, Volume and Issue: 6

Published: Nov. 13, 2018

Autophagy, a cellular homeostatic process, which ensures survival under various stress conditions, has catapulted to the forefront of innate defense mechanisms during intracellular infections. The ability autophagy tag and target pathogens towards lysosomal degradation is central this key function. However, studies involving role regulation infections largely tend ignore housekeeping function autophagy. A growing number evidences now suggest that autophagy, rather than direct pathogen function, may play decisive determine outcome infection immunological balance. We discuss herein establish anti-inflammatory as well bacterial effectors in modulating coopting these functions. Given core machinery remains same across diverse cargos, how selectivity plays out intriguing. explore here, contrasting adaptors being both selective pleotropic functions whether E3 ligases could bring specificity cargo selectivity.

Language: Английский

---