Location, location, location: subcellular protein partitioning in proteostasis and aging

Abstract

Somatic maintenance and cell survival rely on proper protein homeostasis to ensure reliable functions across the cell and to prevent proteome collapse. Maintaining protein folding and solubility is central to proteostasis and is coordinated by protein synthesis, chaperoning, and degradation capacities. An emerging aspect that influences proteostasis is the dynamic protein partitioning across different subcellular structures and compartments. Here, we review recent literature related to nucleocytoplasmic partitioning of proteins, nuclear and cytoplasmic quality control mechanisms, and their impact on the development of age-related diseases. We also highlight new points of entry to modulate spatially-regulated proteostatic mechanisms to delay aging.

Unorthodox localization of P2X7 receptor in subcellular compartments of skeletal system cells

“…Changing the location of a protein can modify its activity, which will modulate its functions and affect its fate. At the same time, subcellular mis-localization of certain proteins is correlated with the onset of specific human pathologies, and may be a hallmark of disease ( Andrejew et al, 2020 ; Kumar and Lapierre, 2021 ; Yousefi et al, 2021 ). Surprisingly, analysis of changes of subcellular protein localization is currently much under investigated compared to the mere study of their expression levels.…”

Special Issue “Deployment of Proteomics Approaches in Biomedical Research”

“…Many angles of personalized medicine, such as diagnostic improvements, systems biology [1], drug screening/mechanisms of action [2,3] and bioinformatics, require the deployment of quantitatively precise human proteomics datasets to make omics analysis actionable at a clinical level [4][5][6]. Biomedical proteomics implements protein research to elucidate disease-affected proteotypes and to determine protein features such as origin, localization [7,8], interactions [9][10][11], posttranslational modifications [12][13][14][15] and protein imbalance [16,17] in human malignancies. Multiple contributions were submitted to this Special Issue, with four original articles and two reviews being accepted for publication.…”

Untitled

“…In C. elegans, the localization and activity of HLH-30 is modulated by the major nutrient sensing mTORC1 complex [1,4] and the nuclear export protein XPO1 [5,6]. Nuclear localization of longevity-associated transcription factors is a feature of many long-lived models in C. elegans, including the quintessential insulin/IGF-1 receptor daf-2 mutants [7]. In the nucleus, HLH-30 can interact with various proteins and transcription factors to generate different transcriptional signatures.…”