Global analysis of aging-related protein structural changes uncovers enzyme-polymerization-based control of longevity.

Aging is associated with progressive phenotypic changes. Virtually all cellular phenotypes are produced by proteins, and their structural alterations can lead to age-related diseases. However, we still lack comprehensive knowledge of proteins undergoing structural-functional changes during cellular aging and their contributions to age-related phenotypes.

Protein aggregation: A detrimental symptom or an adaptation mechanism?

Protein quality control mechanisms oversee numerous aspects of protein lifetime. From the point of protein synthesis, protein homeostasis machineries take part in folding, solubilization, and/or degradation of impaired proteins. Some proteins follow an alternative path upon loss of their solubility, thus are secluded from the cytosol and form protein aggregates.

Lack of peroxisomal catalase affects heat shock response in .

Exact mechanisms of heat shock-induced lifespan extension, although documented across species, are still not well understood. Here, we show that fully functional peroxisomes, specifically peroxisomal catalase, are needed for the activation of canonical heat shock response and heat-induced hormesis in Although during heat shock, the HSP-70 chaperone is strongly up-regulated in the WT and in the absence of peroxisomal catalase (), the small heat shock proteins display modestly increased expression in the mutant. Nuclear foci formation of HSF-1 is reduced in the mutant.

CORE at the boundary of stress resistance and longevity.

As chronological age of an organism increases, a number of errors accumulate at different levels of biological organization. The tendency of errors to accumulate and cause downstream problems in maintenance of cellular homeostasis is met by numerous protection and repair mechanisms. Maintenance of proteins is vital for cell viability and longevity, thus cellular proteostasis is supported by chaperone networks in every cellular compartment, as well as other pathways ensuring timely chaperone expression and activity.

Editorial for the Special Issue "Adaptation, Aging, and Cell Death in Yeast Stress Response: Models, Mechanisms and Applications".

Every cell experiences different types of stress during its life cycle [...

In silico analysis of the aggregation propensity of the SARS-CoV-2 proteome: Insight into possible cellular pathologies.

The SARS-CoV-2 virus causes the coronavirus disease 19 emerged in 2020. The pandemic triggered a turmoil in public health and is having a tremendous social and economic impact around the globe. Upon entry into host cells, the SARS-CoV-2 virus hijacks cellular machineries to produce and maintain its own proteins, spreading the infection.

Functionalized Au nanoclusters as luminescent probes for protein carbonylation detection.

Atomically precise, ligand-protected gold nanoclusters (AuNCs) attract considerable attention as contrast agents in the biosensing field. However, the control of their optical properties and functionalization of surface ligands remain challenging. Here we report a strategy to tailor AuNCs for the precise detection of protein carbonylation-a causal biomarker of ageing.

ATP hydrolysis by yeast Hsp104 determines protein aggregate dissolution and size in vivo.

Signs of proteostasis failure often entwine with those of metabolic stress at the cellular level. Here, we study protein sequestration during glucose deprivation-induced ATP decline in Saccharomyces cerevisiae. Using live-cell imaging, we find that sequestration of misfolded proteins and nascent polypeptides into two distinct compartments, stress granules, and Q-bodies, is triggered by the exhaustion of ATP.

SARS-CoV-2, immunosenescence and inflammaging: partners in the COVID-19 crime.

Pneumonia outbreak in the city of Wuhan, China, prompted the finding of a novel strain of severe acute respiratory syndrome virus (SARS-CoV-2). Here, we discuss potential long-term consequences of SARS-CoV-2 infection, and its possibility to cause permanent damage to the immune system and the central nervous system. Advanced chronological age is one of the main risk factors for the adverse outcomes of COVID-19, presumably due to immunosenescence and chronic low-grade inflammation, both characteristic of the elderly.

Protein damage, ageing and age-related diseases.

Ageing is considered as a snowballing phenotype of the accumulation of damaged dysfunctional or toxic proteins and silent mutations (polymorphisms) that sensitize relevant proteins to oxidative damage as inborn predispositions to age-related diseases. Ageing is not a disease, but it causes (or shares common cause with) age-related diseases as suggested by similar slopes of age-related increase in the incidence of diseases and death. Studies of robust and more standard species revealed that dysfunctional oxidatively damaged proteins are the root cause of radiation-induced morbidity and mortality.

Heat-induced longevity in budding yeast requires respiratory metabolism and glutathione recycling.

Heat-induced hormesis is a well-known conserved phenomenon in aging, traditionally attributed to the benefits conferred by increased amounts of heat shock (HS) proteins. Here we find that the key event for the HS-induced lifespan extension in budding yeast is the switch from glycolysis to respiratory metabolism. The resulting increase in reactive oxygen species activates the antioxidant response, supported by the redirection of glucose from glycolysis to the pentose phosphate pathway, increasing the production of NADPH.

Normal mitochondrial function in has become dependent on inefficient splicing.

Self-splicing introns are mobile elements that have invaded a number of highly conserved genes in prokaryotic and organellar genomes. Here, we show that deletion of these selfish elements from the mitochondrial genome is stressful to the host. A strain without mitochondrial introns displays hallmarks of the retrograde response, with altered mitochondrial morphology, gene expression and metabolism impacting growth and lifespan.

TORC1-mediated sensing of chaperone activity alters glucose metabolism and extends lifespan.

Protein quality control mechanisms, required for normal cellular functioning, encompass multiple functions related to protein production and maintenance. However, the existence of communication between proteostasis and metabolic networks and its underlying mechanisms remain elusive. Here, we report that enhanced chaperone activity and consequent improved proteostasis are sensed by TORC1 via the activity of Hsp82.

The landscape of microbial phenotypic traits and associated genes.

Bacteria and Archaea display a variety of phenotypic traits and can adapt to diverse ecological niches. However, systematic annotation of prokaryotic phenotypes is lacking. We have therefore developed ProTraits, a resource containing ∼545 000 novel phenotype inferences, spanning 424 traits assigned to 3046 bacterial and archaeal species.

Crosstalk between cellular compartments protects against proteotoxicity and extends lifespan.

In cells living under optimal conditions, protein folding defects are usually prevented by the action of chaperones. Here, we investigate the cell-wide consequences of loss of chaperone function in cytosol, mitochondria or the endoplasmic reticulum (ER) in budding yeast. We find that the decline in chaperone activity in each compartment results in loss of respiration, demonstrating the dependence of mitochondrial activity on cell-wide proteostasis.

Decreasing translation error rate in Escherichia coli increases protein function.

Background: Over-expressed native or recombinant proteins are commonly used for industrial and pharmaceutical purposes, as well as for research. Proteins of interest need to be purified in sufficient quantity, quality and specific activity to justify their commercial price and eventual medical use. Proteome quality was previously positively correlated with ribosomal fidelity, but not on a single protein level.

Global Shifts in Genome and Proteome Composition Are Very Tightly Coupled.

The amino acid composition (AAC) of proteomes differs greatly between microorganisms and is associated with the environmental niche they inhabit, suggesting that these changes may be adaptive. Similarly, the oligonucleotide composition of genomes varies and may confer advantages at the DNA/RNA level. These influences overlap in protein-coding sequences, making it difficult to gauge their relative contributions.

RNA chaperones buffer deleterious mutations in E. coli.

Both proteins and RNAs can misfold into non-functional conformations. Protein chaperones promote native folding of nascent polypeptides and refolding of misfolded species, thereby buffering mutations that compromise protein structure and function. Here, we show that RNA chaperones can also act as mutation buffers that enhance organismal fitness.