Winter is coming: Regulation of cellular metabolism by enzyme polymerization in dormancy and disease

Montrose, Kristopher; Cabezas, Rosa María López; Paukštytė, Jurgita; Saarikangas, Juha

doi:10.1016/j.yexcr.2020.112383

Cited by 6 publications

(3 citation statements)

References 248 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several metabolic enzymes undergo reversible polymerization as an adaptive response to changes in the environment 59,60 . We considered whether age-related Glt1 polymerization is an adaptation that impacts cellular longevity.…”

Section: Inhibiting Glt1 Polymerization Delays Aging Prevents Intrace...mentioning

confidence: 99%

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

Paukštytė

Cabezas

Feng

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Aging is associated with progressive phenotypic changes over time. Virtually all cellular phenotypes are produced by proteins and structural alterations in proteins can lead to age-related diseases. Nonetheless, comprehensive knowledge of proteins undergoing structural-functional changes during cellular aging and their contribution to age-related phenotypes is lacking. Here, we conducted proteome-wide analysis of early age-related protein structural changes in budding yeast using limited proteolysis-mass spectrometry. The results, compiled in online ProtAge-catalog, unravelled age-related functional changes in regulators of translation, protein folding and amino acid metabolism. Mechanistically, we found that folded glutamate synthase Glt1 polymerizes into supramolecular self-assemblies during aging causing breakdown of cellular amino acid homeostasis. Inhibiting Glt1 polymerization by mutating the polymerization interface restored amino acid levels in aged cells, attenuated mitochondrial dysfunction and led to life span extension. Altogether, this comprehensive map of protein structural changes enables identifying novel mechanisms of age-related phenotypes and offers opportunities for their reversal.

show abstract

Section: Inhibiting Glt1 Polymerization Delays Aging Prevents Intrace...mentioning

confidence: 99%

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

Paukštytė

Cabezas

Feng

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…We recommend referring to Park and Horton’s review (Park and Horton 2019 ) for an exhaustive review of protein filamentation. We also recommend referring to recent reviews tackling how agglomeration can regulate enzymatic activity (Garcia-Seisdedos et al 2019 ; Hvorecny and Kollman 2023 ; Liu 2016 ; Lynch et al 2020 ; Montrose et al 2020 ). Here, we give a brief overview of how agglomeration regulates the activity of some enzymes and how agglomeration can promote cellular dormancy (Montrose et al 2020 ; Munder et al 2016 ).…”

Section: Agglomeration In Evolutionmentioning

confidence: 99%

“…Changes in the intracellular environment can also trigger metabolic enzymes to assemble into filaments (Munder et al 2016 ; Narayanaswamy et al 2009 ; Park and Horton 2019 ; Petrovska et al 2014 ). These assemblies appear to serve various functions, such as regulating enzymatic activity (Kim et al 2010 ; Stoddard et al 2020 ), preventing degradation (Petrovska et al 2014 ), promoting cellular dormancy (Montrose et al 2020 ), and, in some cases, being associated with aging (Paukštytė et al 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Agglomeration: when folded proteins clump together

Romero-Romero,

Garcia-Seisdedos

2023

Biophys Rev

View full text Add to dashboard Cite

Protein self-association is a widespread phenomenon that results in the formation of multimeric protein structures with critical roles in cellular processes. Protein self-association can lead to finite protein complexes or open-ended, and potentially, infinite structures. This review explores the concept of protein agglomeration, a process that results from the infinite self-assembly of folded proteins. We highlight its differences from other better-described processes with similar macroscopic features, such as aggregation and liquid-liquid phase separation. We review the sequence, structural, and biophysical factors influencing protein agglomeration. Lastly, we briefly discuss the implications of agglomeration in evolution, disease, and aging. Overall, this review highlights the need to study protein agglomeration for a better understanding of cellular processes.

show abstract

Liquid–liquid phase separation and biomolecular condensates in cell quiescence

Uversky

2023

Droplets of Life

View full text Add to dashboard Cite

Winter is coming: Regulation of cellular metabolism by enzyme polymerization in dormancy and disease

Cited by 6 publications

References 248 publications

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

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

Agglomeration: when folded proteins clump together

Liquid–liquid phase separation and biomolecular condensates in cell quiescence

Contact Info

Product

Resources

About