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Book ; Online ; Thesis: Protein aggregation in the cytoplasm

Amen, Triana [Verfasser]

2020

Author's details	Triana Amen
Keywords	Biowissenschaften, Biologie ; Life Science, Biology
Subject code	sg570
Language	English
Publisher	Niedersächsische Staats- und Universitätsbibliothek Göttingen
Publishing place	Göttingen
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article: Small Molecule Screen Reveals Joint Regulation of Stress Granule Formation and Lipid Droplet Biogenesis.

Amen, Triana / Kaganovich, Daniel

Frontiers in cell and developmental biology

2021 Volume 8, Page(s) 606111

Abstract: Metabolic regulation is a necessary component of all stress response pathways, because all different mechanisms of stress-adaptation place high-energy demands on the cell. Mechanisms that integrate diverse stress response pathways with their metabolic ... ...

Abstract	Metabolic regulation is a necessary component of all stress response pathways, because all different mechanisms of stress-adaptation place high-energy demands on the cell. Mechanisms that integrate diverse stress response pathways with their metabolic components are therefore of great interest, but few are known. We show that stress granule (SG) formation, a common adaptive response to a variety of stresses, is reciprocally regulated by the pathways inducing lipid droplet accumulation. Inability to upregulate lipid droplets reduces stress granule formation. Stress granule formation in turn drives lipid droplet clustering and fatty acid accumulation. Our findings reveal a novel connection between stress response pathways and new modifiers of stress granule formation.
Language	English
Publishing date	2021-04-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2020.606111
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Stress granules inhibit fatty acid oxidation by modulating mitochondrial permeability.

Amen, Triana / Kaganovich, Daniel

Cell reports

2021 Volume 35, Issue 11, Page(s) 109237

Abstract: The formation of stress granules (SGs) is an essential aspect of the cellular response to many kinds of stress, but its adaptive role is far from clear. SG dysfunction is implicated in aging-onset neurodegenerative diseases, prompting interest in their ... ...

Abstract	The formation of stress granules (SGs) is an essential aspect of the cellular response to many kinds of stress, but its adaptive role is far from clear. SG dysfunction is implicated in aging-onset neurodegenerative diseases, prompting interest in their physiological function. Here, we report that during starvation stress, SGs interact with mitochondria and regulate metabolic remodeling. We show that SG formation leads to a downregulation of fatty acid β-oxidation (FAO) through the modulation of mitochondrial voltage-dependent anion channels (VDACs), which import fatty acids (FAs) into mitochondria. The subsequent decrease in FAO during long-term starvation reduces oxidative damage and rations FAs for longer use. Failure to form SGs, whether caused by the genetic deletion of SG components or an amyotrophic lateral sclerosis (ALS)-associated mutation, translates into an inability to downregulate FAO. Because metabolic dysfunction is a common pathological element of neurodegenerative diseases, including ALS, our findings provide a direction for studying the clinical relevance of SGs.
MeSH term(s)	Amyotrophic Lateral Sclerosis/pathology ; Cell Line, Tumor ; Cell Lineage ; Fatty Acids/metabolism ; HEK293 Cells ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Lipid Droplets/metabolism ; Mitochondria/metabolism ; Neurons/pathology ; Oxidation-Reduction ; Permeability ; Starvation ; Stress Granules/metabolism
Chemical Substances	Fatty Acids
Language	English
Publishing date	2021-08-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2021.109237
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Article ; Online: Small Molecule Screen Reveals Joint Regulation of Stress Granule Formation and Lipid Droplet Biogenesis

Triana Amen / Daniel Kaganovich

Frontiers in Cell and Developmental Biology, Vol

2021 Volume 8

Abstract	Metabolic regulation is a necessary component of all stress response pathways, because all different mechanisms of stress-adaptation place high-energy demands on the cell. Mechanisms that integrate diverse stress response pathways with their metabolic components are therefore of great interest, but few are known. We show that stress granule (SG) formation, a common adaptive response to a variety of stresses, is reciprocally regulated by the pathways inducing lipid droplet accumulation. Inability to upregulate lipid droplets reduces stress granule formation. Stress granule formation in turn drives lipid droplet clustering and fatty acid accumulation. Our findings reveal a novel connection between stress response pathways and new modifiers of stress granule formation.
Keywords	stress granule ; lipid droplet ; PPAR ; lipid metabolism ; fatty acids ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Stress granules inhibit fatty acid oxidation by modulating mitochondrial permeability

Triana Amen / Daniel Kaganovich

Cell Reports, Vol 35, Iss 11, Pp 109237- (2021)

2021

Abstract: Summary: The formation of stress granules (SGs) is an essential aspect of the cellular response to many kinds of stress, but its adaptive role is far from clear. SG dysfunction is implicated in aging-onset neurodegenerative diseases, prompting interest ... ...

Abstract	Summary: The formation of stress granules (SGs) is an essential aspect of the cellular response to many kinds of stress, but its adaptive role is far from clear. SG dysfunction is implicated in aging-onset neurodegenerative diseases, prompting interest in their physiological function. Here, we report that during starvation stress, SGs interact with mitochondria and regulate metabolic remodeling. We show that SG formation leads to a downregulation of fatty acid β-oxidation (FAO) through the modulation of mitochondrial voltage-dependent anion channels (VDACs), which import fatty acids (FAs) into mitochondria. The subsequent decrease in FAO during long-term starvation reduces oxidative damage and rations FAs for longer use. Failure to form SGs, whether caused by the genetic deletion of SG components or an amyotrophic lateral sclerosis (ALS)-associated mutation, translates into an inability to downregulate FAO. Because metabolic dysfunction is a common pathological element of neurodegenerative diseases, including ALS, our findings provide a direction for studying the clinical relevance of SGs.
Keywords	stress granule ; lipid metabolism ; fatty acid oxidation ; VDAC ; mitochondria ; porin ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Fasnall Induces Atypically Transient Stress Granules Independently of FASN Inhibition.

Amen, Triana / Kaganovich, Daniel

iScience

2020 Volume 23, Issue 10, Page(s) 101550

Abstract: Stress Granule formation has been linked to the resistance of some cancer cells to chemotherapeutic intervention. A number of studies have proposed that certain anti-tumor compounds promote cancer cell survival by inducing Stress Granule formation, ... ...

Abstract	Stress Granule formation has been linked to the resistance of some cancer cells to chemotherapeutic intervention. A number of studies have proposed that certain anti-tumor compounds promote cancer cell survival by inducing Stress Granule formation, leading to increased cellular fitness and apoptosis avoidance. Here we show that a potent fatty acid synthase inhibitor, fasnall, known for its anti-tumor capabilities, triggers the formation of atypical Stress Granules, independently of fatty acid synthase inhibition, characterized by high internal mobility and rapid turnover.
Language	English
Publishing date	2020-09-10
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2020.101550
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Quantitative photoconversion analysis of internal molecular dynamics in stress granules and other membraneless organelles in live cells.

Amen, Triana / Kaganovich, Daniel

STAR protocols

2020 Volume 1, Issue 3, Page(s) 100217

Abstract: ... execution of this protocol, please refer to Amen and Kaganovich (2020). ...

Abstract	Photoconversion enables real-time labeling of protein sub-populations inside living cells, which can then be tracked with submicrometer resolution. Here, we detail the protocol of comparing protein dynamics inside membraneless organelles in live HEK293T cells using a CRISPR-Cas9 PABPC1-Dendra2 marker of stress granules. Measuring internal dynamics of membraneless organelles provides insight into their functional state, physical properties, and composition. Photoconversion has the advantage over other imaging techniques in that it is less phototoxic and allows for dual color tracking of proteins. For complete details on the use and execution of this protocol, please refer to Amen and Kaganovich (2020).
MeSH term(s)	Benzothiazoles/chemistry ; Biomolecular Condensates/metabolism ; Biomolecular Condensates/physiology ; HEK293 Cells ; Humans ; Molecular Dynamics Simulation ; Molecular Probe Techniques/instrumentation ; Molecular Probes/chemistry ; Molecular Probes/genetics ; Optical Imaging/methods ; Organelles/metabolism ; Proteins/metabolism ; Stress Granules/metabolism ; Stress Granules/physiology
Chemical Substances	Benzothiazoles ; Molecular Probes ; Proteins ; fluorescence probe E1
Language	English
Publishing date	2020-12-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2020.100217
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Stress granules sense metabolic stress at the plasma membrane and potentiate recovery by storing active Pkc1.

Amen, Triana / Kaganovich, Daniel

Science signaling

2020 Volume 13, Issue 623

Abstract: As the physical barrier between the cell and the outside environment, the plasma membrane is well-positioned to be the first responder to stress. The membrane is also highly vulnerable to many types of perturbation, including heat, force, osmotic ... ...

Abstract	As the physical barrier between the cell and the outside environment, the plasma membrane is well-positioned to be the first responder to stress. The membrane is also highly vulnerable to many types of perturbation, including heat, force, osmotic pressure, lipid shortage, and starvation. To determine whether the structural changes in the plasma membrane of
MeSH term(s)	Cell Membrane/metabolism ; Cytoplasmic Granules/genetics ; Cytoplasmic Granules/metabolism ; Mass Spectrometry/methods ; Microscopy, Confocal/methods ; Mutation ; Phosphoproteins/genetics ; Phosphoproteins/metabolism ; Protein Kinase C/genetics ; Protein Kinase C/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Signal Transduction/genetics ; Stress, Physiological
Chemical Substances	PIL1 protein, S cerevisiae ; Phosphoproteins ; Saccharomyces cerevisiae Proteins ; PKC1 protein, S cerevisiae (EC 2.7.11.13) ; Protein Kinase C (EC 2.7.11.13)
Language	English
Publishing date	2020-03-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2417226-1
ISSN	1937-9145 ; 1945-0877
ISSN (online)	1937-9145
ISSN	1945-0877
DOI	10.1126/scisignal.aaz6339
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Quantitative photoconversion analysis of internal molecular dynamics in stress granules and other membraneless organelles in live cells

Triana Amen / Daniel Kaganovich

STAR Protocols, Vol 1, Iss 3, Pp 100217- (2020)

2020

Abstract: ... execution of this protocol, please refer to Amen and Kaganovich (2020). ...

Abstract	Summary: Photoconversion enables real-time labeling of protein sub-populations inside living cells, which can then be tracked with submicrometer resolution. Here, we detail the protocol of comparing protein dynamics inside membraneless organelles in live HEK293T cells using a CRISPR-Cas9 PABPC1-Dendra2 marker of stress granules. Measuring internal dynamics of membraneless organelles provides insight into their functional state, physical properties, and composition. Photoconversion has the advantage over other imaging techniques in that it is less phototoxic and allows for dual color tracking of proteins.For complete details on the use and execution of this protocol, please refer to Amen and Kaganovich (2020).
Keywords	Cell Biology ; Microscopy ; CRISPR ; Molecular/Chemical Probes ; Science (General) ; Q1-390
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Fasnall Induces Atypically Transient Stress Granules Independently of FASN Inhibition

Triana Amen / Daniel Kaganovich

iScience, Vol 23, Iss 10, Pp 101550- (2020)

2020

Abstract: Summary: Stress Granule formation has been linked to the resistance of some cancer cells to chemotherapeutic intervention. A number of studies have proposed that certain anti-tumor compounds promote cancer cell survival by inducing Stress Granule ... ...

Abstract	Summary: Stress Granule formation has been linked to the resistance of some cancer cells to chemotherapeutic intervention. A number of studies have proposed that certain anti-tumor compounds promote cancer cell survival by inducing Stress Granule formation, leading to increased cellular fitness and apoptosis avoidance. Here we show that a potent fatty acid synthase inhibitor, fasnall, known for its anti-tumor capabilities, triggers the formation of atypical Stress Granules, independently of fatty acid synthase inhibition, characterized by high internal mobility and rapid turnover.
Keywords	Biomolecules ; Cell Biology ; Cancer ; Science ; Q
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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