A huge amount of intrigue surrounds the aging process. Senescence—the decreased likelihood of reproduction and the increased chance of mortality—is a hallmark of aging. The reduced ability of senescent cells to maintain protein homeostasis (proteostasis) has been well-established in nematodes but this phenomenon had yet to be directly demonstrated in human cells. Sabath et al. recently provided compelling evidence that proteostasis collapse is indeed intrinsic to human cell senescence, which may have broad implications in the underlying processes of human aging.
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http://dx.doi.org/10.1038/s42003-020-01578-w | DOI Listing |
Cellular systems that govern protein folding rely on a delicate balance of functional redundancy and diversification to maintain protein homeostasis (proteostasis). Here, we use to demonstrate how both overlapping and divergent activities of two homologous endoplasmic reticulum (ER)-resident HSP70 family chaperones, HSP-3 and HSP-4, orchestrate ER proteostasis and contribute to organismal physiology. We identify tissue-, age-, and stress-specific protein expression patterns and find both redundant and distinct functions for HSP-3 and HSP-4 in ER stress resistance, reproduction, and body size regulation.
View Article and Find Full Text PDFACS Cent Sci
January 2025
The Rosalind Franklin Institute, Harwell Science & Innovation Campus, Harwell OX11 0FA, U.K.
Protein N-glycosylation is a cotranslational modification that takes place in the endoplasmic reticulum (ER). Disruption of this process can result in accumulation of misfolded proteins, known as ER stress. In response, the unfolded protein response (UPR) restores proteostasis or responds by controlling cellular fate, including increased expression of activating transcription factor 4 (ATF4) that can lead to apoptosis.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Biological Sciences, Dedman College of Humanities and Sciences, Southern Methodist University, Dallas, TX, 75275, USA.
The 40S ribosomal subunit recycling pathway is an integral link in the cellular quality control network, occurring after translational errors have been corrected by the ribosome-associated quality control (RQC) machinery. Despite our understanding of its role, the impact of translation quality control on cellular metabolism remains poorly understood. Here, we reveal a conserved role of the 40S ribosomal subunit recycling (USP10-G3BP1) complex in regulating mitochondrial dynamics and function.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of General and Medical Biochemistry, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland.
Plant pathogenic bacteria are responsible for a substantial number of plant diseases worldwide, resulting in significant economic losses. Bacteria are exposed to numerous stress factors during their epiphytic life and within the host. Their ability to survive in the host and cause symptomatic infections depends on their capacity to overcome stressors.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Laboratorio de Biología de la Reproducción, Departamento Biomédico, Facultad de Ciencias de la Salud, Universidad de Antofagasta, Antofagasta 1240000, Chile.
Proteasome-mediated protein degradation is essential for maintaining cellular homeostasis, particularly during spermatogenesis, where extensive cellular transformations, such as spermatid differentiation, require precise protein turnover. A key player in this process is the ubiquitin-proteasome system (UPS). This study aimed to investigate proteasome enzymatic activity at different stages of the spermatogenic cycle within the seminiferous tubules of mice and explore the regulatory mechanisms that influence its proteolytic function.
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