mTOR Signaling in Growth Control and Disease

Cell, Journal Year: 2012, Volume and Issue: 149(2), P. 274 - 293

Published: April 1, 2012

Language: Английский

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Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Autophagy, Journal Year: 2016, Volume and Issue: 12(1), P. 1 - 222

Published: Jan. 2, 2016

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, on this topic has continued to accelerate, and many new scientists have entered field. Our knowledge base relevant technologies also been expanding. Accordingly, it is important update these monitoring autophagy different organisms. Various reviews described range assays that used purpose. Nevertheless, there continues be confusion regarding acceptable methods measure autophagy, especially multicellular eukaryotes. For example, a key point needs emphasized difference between measurements monitor numbers or volume autophagic elements (e.g., autophagosomes autolysosomes) at any stage process versus those flux through pathway (i.e., complete including amount rate cargo sequestered degraded). particular, block macroautophagy results autophagosome accumulation must differentiated from stimuli increase activity, defined as increased induction coupled with delivery to, degradation within, lysosomes (in most higher eukaryotes some protists such Dictyostelium) vacuole plants fungi). other words, investigators field understand appearance more does not necessarily equate fact, cases, accumulate because trafficking without concomitant change biogenesis, whereas an autolysosomes may reflect reduction degradative activity. It worth emphasizing here lysosomal digestion evaluating its competence crucial part evaluation flux, autophagy. Here, present selection interpretation use by who aim examine related processes, well reviewers need provide realistic reasonable critiques papers are focused processes. These meant formulaic rules, appropriate depend question being asked system used. addition, emphasize no individual assay guaranteed one every situation, strongly recommend multiple Along lines, potential pleiotropic effects due blocking genetic manipulation, imperative target gene knockout RNA interference than autophagy-related protein. Atg proteins, groups involved cellular pathways implying all proteins can specific marker process. guidelines, consider various assessing what information can, cannot, obtained them. Finally, discussing merits limits particular assays, hope encourage technical innovation

Language: Английский

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Guidelines for the use and interpretation of assays for monitoring autophagy

Autophagy, Journal Year: 2012, Volume and Issue: 8(4), P. 445 - 544

Published: April 1, 2012

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, on this topic has continued to accelerate, and many new scientists have entered field. Our knowledge base relevant technologies also been expanding. Accordingly, it is important update these monitoring autophagy different organisms. Various reviews described range assays that used purpose. Nevertheless, there continues be confusion regarding acceptable methods measure autophagy, especially multicellular eukaryotes. A key point needs emphasized a difference between measurements monitor numbers or volume autophagic elements (e.g., autophagosomes autolysosomes) at any stage process vs. those flux through pathway (i.e., complete process); thus, block macroautophagy results autophagosome accumulation differentiated from stimuli result increased activity, defined as induction coupled with delivery to, degradation within, lysosomes (in most higher eukaryotes some protists such Dictyostelium) vacuole plants fungi). other words, investigators field understand appearance more does not necessarily equate fact, cases, accumulate because trafficking without concomitant change biogenesis, whereas an increase autolysosomes may reflect reduction degradative activity. Here, present selection interpretation use by who aim examine related processes, well reviewers need provide realistic reasonable critiques papers are focused processes. These meant formulaic rules, appropriate depend part question being asked system used. addition, emphasize no individual assay guaranteed one every situation, strongly recommend multiple guidelines, consider various assessing what information can, cannot, obtained them. Finally, discussing merits limits particular assays, hope encourage technical innovation

Language: Английский

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Antimicrobial Autophagy: A Conserved Innate Immune Response in Drosophila

Journal of Innate Immunity, Journal Year: 2013, Volume and Issue: 5(5), P. 444 - 455

Published: Jan. 1, 2013

Autophagy is a major route by which cytoplasmic contents are delivered to the lysosome for degradation. Many autophagy-related (ATG) genes have been identified in yeast. Although most of them conserved human, molecular composition Atg1 complex appears differ between yeast and mammals. In yeast, forms with Atg11, Atg13, Atg17, Atg29 Atg31, whereas mammalian (ULK1/2) interacts Atg13 FIP200. Here, we identify novel binding protein, named Atg101. Atg101 shows no homology other Atg proteins, various eukaryotes, but not Saccharomyces cerevisiae. associates ULK-Atg13-FIP200 complex, likely through direct interaction Atg13. siRNA-treated cells, present solely as monomer. Interaction stable, regulated nutrient conditions. GFP-Atg101 localizes isolation membrane/phagophore. GFP-LC3 dot formation suppressed endogenous LC3-I accumulates suggesting that critical factor autophagy. Furthermore, important stability basal phosphorylation ULK1. These data suggest protein functions together ULK,

Language: Английский

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AMPK: guardian of metabolism and mitochondrial homeostasis

Nature Reviews Molecular Cell Biology, Journal Year: 2017, Volume and Issue: 19(2), P. 121 - 135

Published: Oct. 4, 2017

Language: Английский

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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

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mTOR: a pharmacologic target for autophagy regulation

Journal of Clinical Investigation, Journal Year: 2015, Volume and Issue: 125(1), P. 25 - 32

Published: Jan. 1, 2015

mTOR, a serine/threonine kinase, is master regulator of cellular metabolism. mTOR regulates cell growth and proliferation in response to wide range cues, its signaling pathway deregulated many human diseases. also plays crucial role regulating autophagy. This Review provides an overview the pathway, mechanisms autophagy regulation, clinical implications inhibitors disease treatment.

Language: Английский

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A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB

The EMBO Journal, Journal Year: 2012, Volume and Issue: 31(5), P. 1095 - 1108

Published: Feb. 17, 2012

Language: Английский

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Mitophagy and Quality Control Mechanisms in Mitochondrial Maintenance

Current Biology, Journal Year: 2018, Volume and Issue: 28(4), P. R170 - R185

Published: Feb. 1, 2018

Language: Английский

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Signals from the lysosome: a control centre for cellular clearance and energy metabolism

Nature Reviews Molecular Cell Biology, Journal Year: 2013, Volume and Issue: 14(5), P. 283 - 296

Published: April 23, 2013

Language: Английский

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