The Effect of Calorie Restriction on Protein Quality Control in Yeast DOI Creative Commons

Petter Uvdal,

Sviatlana Shashkova

Biomolecules, Journal Year: 2023, Volume and Issue: 13(5), P. 841 - 841

Published: May 15, 2023

Initially, protein aggregates were regarded as a sign of pathological state the cell. Later, it was found that these assemblies are formed in response to stress, and some them serve signalling mechanisms. This review has particular focus on how intracellular related altered metabolism caused by different glucose concentrations extracellular environment. We summarise current knowledge role energy homeostasis pathways consequent effect aggregate accumulation removal. covers regulation at levels, including elevated degradation proteasome activity mediated Hxk2 protein, enhanced ubiquitination aberrant proteins through Torc1/Sch9 Msn2/Whi2, activation autophagy ATG genes. Finally, certain form reversible biomolecular stress reduced which used mechanism cell, controlling major primary sensing.

Language: Английский

The Integral Role of RNA in Stress Granule Formation and Function DOI Creative Commons
Danae Campos-Melo,

Zachary C. E. Hawley,

Cristian A. Droppelmann

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: May 20, 2021

Stress granules (SGs) are phase-separated, membraneless, cytoplasmic ribonucleoprotein (RNP) assemblies whose primary function is to promote cell survival by condensing translationally stalled mRNAs, ribosomal components, translation initiation factors, and RNA-binding proteins (RBPs). While the protein composition of in compartmentalization dynamics assembly disassembly SGs has been a matter study for several years, role RNA these structures had remained largely unknown. species are, however, not passive members that itself can form homo heterotypic interactions with other molecules leading phase separation nucleation granules. also as molecular scaffolds recruiting multivalent RBPs their interactors higher-order structures. With development SG purification techniques coupled RNA-seq, transcriptomic landscape becoming increasingly understood, revealing enormous potential guide transient organelles. only formed under acute stress conditions but response different diseases such viral infections, cancer, neurodegeneration. Importantly, being recognized precursors pathological aggregates neurodegenerative diseases. In this review, we examine current evidence support playing significant formation explore concept therapeutic targets.

Language: Английский

Citations

108
Polysome collapse and RNA condensation fluidize the cytoplasm DOI
Ying Xie, Tong Shu,

Tiewei Liu

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(14), P. 2698 - 2716.e9

Published: July 1, 2024

Language: Английский

Citations

9
Engineering a membrane protein chaperone to ameliorate the proteotoxicity of mutant huntingtin DOI Creative Commons
Jeong Hyun Oh,

Christy Catherine,

Eun Seon Kim

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 17, 2025

Toxic protein aggregates are associated with various neurodegenerative diseases, including Huntington's disease (HD). Since no current treatment delays the progression of HD, we develop a mechanistic approach to prevent mutant huntingtin (mHttex1) aggregation. Here, engineer ATP-independent cytosolic chaperone PEX19, which targets peroxisomal membrane proteins peroxisomes, remove mHttex1 aggregates. Using yeast toxicity-based screening random library, identify two PEX19 variants and equivalent mutations into human (hsPEX19). These effectively delay aggregation in vitro cellular HD models. The mutated hydrophobic residue α4 helix hsPEX19 binds N17 domain mHttex1, thereby inhibiting initial process. Overexpression hsPEX19-FV variant rescues HD-associated phenotypes primary striatal neurons Drosophila. Overall, our data reveal that engineering chaperones is promising therapeutic for rational targeting HD.

Language: Английский

Citations

1
Reversible amyloids of pyruvate kinase couple cell metabolism and stress granule disassembly DOI
Gea Cereghetti,

Caroline Wilson-Zbinden,

Vera M. Kissling

et al.

Nature Cell Biology, Journal Year: 2021, Volume and Issue: 23(10), P. 1085 - 1094

Published: Oct. 1, 2021

Language: Английский

Citations

46
Intrinsic factors behind long COVID: IV. Hypothetical roles of the SARS‐CoV‐2 nucleocapsid protein and its liquid–liquid phase separation DOI

Ahmed Eltayeb,

Faisal Al‐Sarraj, Mona G. Alharbi

et al.

Journal of Cellular Biochemistry, Journal Year: 2024, Volume and Issue: 125(3)

Published: Feb. 13, 2024

Abstract When the SARS‐CoV‐2 virus infects humans, it leads to a condition called COVID‐19 that has wide spectrum of clinical manifestations, from no symptoms acute respiratory distress syndrome. The initiates damage by attaching ACE‐2 protein on surface endothelial cells line blood vessels and using these as hosts for replication. Reactive oxygen species levels are increased during viral replication, which oxidative stress. About three‐fifths (~60%) people who get infected with eradicate their body after 28 days recover normal activity. However, large fraction (~40%) suffer various (anosmia and/or ageusia, fatigue, cough, myalgia, cognitive impairment, insomnia, dyspnea, tachycardia) beyond 12 weeks diagnosed syndrome long COVID. Long‐term studies in group contracted have been contrasted noninfected matched people. A subset can be distinguished set cytokine markers persistent, low‐grade inflammation often self‐report two or more bothersome symptoms. No medication alleviate efficiently. Coronavirus nucleocapsid proteins investigated extensively potential drug targets due key roles among is ability bind respective genomic RNAs incorporation into emerging virions. This review highlights basic its undergo liquid–liquid phase separation. We hypothesize this separation may contribute hypothesis unlocks new investigation angles could potentially open novel avenues better understanding COVID treating condition.

Language: Английский

Citations

7
Understanding resource competition to achieve predictable synthetic gene expression in eukaryotes DOI
Roberto Di Blasi, Jacopo Gabrielli, Kiyan Shabestary

et al.

Nature Reviews Bioengineering, Journal Year: 2024, Volume and Issue: 2(9), P. 721 - 732

Published: July 4, 2024

Language: Английский

Citations

5
Melatonin: Regulation of Biomolecular Condensates in Neurodegenerative Disorders DOI Creative Commons
Doris Loh, Rüssel J. Reiter

Antioxidants, Journal Year: 2021, Volume and Issue: 10(9), P. 1483 - 1483

Published: Sept. 17, 2021

Biomolecular condensates are membraneless organelles (MLOs) that form dynamic, chemically distinct subcellular compartments organizing macromolecules such as proteins, RNA, and DNA in unicellular prokaryotic bacteria complex eukaryotic cells. Separated from surrounding environments, MLOs the nucleoplasm, cytoplasm, mitochondria assemble by liquid–liquid phase separation (LLPS) into transient, non-static, liquid-like droplets regulate essential molecular functions. LLPS is primarily controlled post-translational modifications (PTMs) fine-tune balance between attractive repulsive charge states and/or binding motifs of proteins. Aberrant due to dysregulated membrane lipid rafts PTMs, well absence adequate hydrotropic small molecules ATP, or presence specific RNA proteins can cause pathological protein aggregation neurodegenerative disorders. Melatonin may exert a dominant influence over biomolecular optimizing MLO interdependent reactions through stabilizing raft domains, reducing line tension, maintaining negative curvature fluidity. As potent antioxidant, melatonin protects cardiolipin other lipids peroxidation cascades, supporting trafficking, signaling, ion channel activities, ATPase functionality during condensate coacervation dissolution. even control PTM mRNA- RNA-binding composition regulating N6-methyladenosine (m6A) modifications. There currently lack pharmaceuticals targeting disorders via regulation separation. The potential modulation attenuation aberrant discussed this review.

Language: Английский

Citations

30
Regulation of physiological and pathological condensates by molecular chaperones DOI Creative Commons

Nadeen Akaree,

Valentina Secco,

Flonia Levy‐Adam

et al.

FEBS Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 5, 2025

Biomolecular condensates are dynamic membraneless compartments that regulate a myriad of cellular functions. A particular type physiological condensate called stress granules (SGs) has gained increasing interest due to its role in the response and various diseases. SGs, composed several hundred RNA‐binding proteins, form transiently protect mRNAs from translation disassemble when subsides. Interestingly, SGs contain aggregation‐prone such as TDP‐43, FUS, hnRNPA1, others, which typically found pathological inclusions seen autopsy tissues amyotrophic lateral sclerosis (ALS) frontotemporal dementia (FTD) patients. Moreover, mutations these genes lead familial ALS FTD. This led researchers propose aggregation is seeded by aberrant SGs: fail properly disassemble, lose their properties, become finally ‘mature’ into aggregates. Here, we discuss evidence supporting this model for ALS/FTD‐associated proteins. We further continue focus on molecular chaperone‐mediated regulation one hand, other. In addition review ALS/FTD‐relevant nuclear condensates, namely paraspeckles, anisosomes, nucleolar amyloid bodies, emerging chaperones. As majority chaperoning mechanisms disassembly, highlight parallel themes condensation across different chaperone families, underscoring potential early disease intervention.

Language: Английский

Citations

0
MitoStores: stress-induced aggregation of mitochondrial proteins DOI
P. Kaushik, Johannes M. Herrmann, Katja G. Hansen

et al.

Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Abstract Most mitochondrial proteins are synthesized in the cytosol and post-translationally imported into mitochondria. If rate of protein synthesis exceeds capacity import machinery, precursor can transiently accumulate cytosol. The cytosolic accumulation precursors jeopardizes cellular homeostasis (proteostasis) be cause diseases. In order to prevent these toxic effects, most non-imported rapidly degraded by ubiquitin-proteasome system. However, cells employ a second layer defense which is facilitated sequestration transient aggregates. formation such structures triggered nucleation factors as small heat shock proteins. Disaggregases chaperones liberate from aggregates pass them on machinery or, under persistent stress conditions, proteasome for degradation. Owing their role buffering systems, were referred MitoStores. This review articles provides general overview about MitoStore concept early stages biogenesis yeast and, cases where aspects differ, mammalian cells.

Language: Английский

Citations

0
Stress granules: emerging players in neurodegenerative diseases DOI Creative Commons
Lin Yuan,

Lihong Mao,

Yanming Huang

et al.

Translational Neurodegeneration, Journal Year: 2025, Volume and Issue: 14(1)

Published: May 12, 2025

Abstract Stress granules (SGs) are membraneless organelles formed in the cellular cytoplasm under stressful conditions through liquid–liquid phase separation (LLPS). SG assembly can be both dependent and independent of eIF2α pathway, whereas protein quality control systems mediate disassembly. Chaperones specific domains RNA-binding proteins strongly contribute to regulation dynamics. Chronic stress, arising association with aging, may promote persistent SGs that difficult disassemble, thereby acting as a potential pathological nidus for aggregation neurodegenerative diseases (NDDs). In this review, we discuss dynamics factors involved We also highlight relationship among LLPS, SGs, pathogenesis different NDDs. More importantly, summarize assembly-disassembly, which double-edged sword pathophysiology This review aims provide new insights into biology pathology

Language: Английский

Citations

0