The ubiquitin-proteasome system is crucial for proteostasis, particularly during proteotoxic stress. The interaction between heat shock protein (HSP) 70 and the ubiquitin ligase CHIP plays a key role in this process. Our study investigates the Caenorhabditis elegans orthologs HSP-1 and CHN-1, demonstrating that HSP-1 binding decreases CHN-1 E3 ligase activity, aligning with the inhibitory effects observed in human HSP70-CHIP interactions.
View Article and Find Full Text PDFMechanical stress during muscle contraction is a constant threat to proteome integrity. However, there is a lack of experimental systems to identify critical proteostasis regulators under mechanical stress conditions. Here, we present the transgenic Caenorhabditis elegans model OptIMMuS (Optogenetic Induction of Mechanical Muscle Stress) to study changes in the proteostasis network associated with mechanical forces.
View Article and Find Full Text PDFThe degradation of damaged proteins is critical for tissue integrity and organismal health because damaged proteins have a high propensity to form aggregates. E3 ubiquitin ligases are key regulators of protein quality control (PQC) and mediate the selective degradation of damaged proteins, a process termed 'PQC degradation' (PQCD). The degradation signals (degrons) that trigger PQCD are based on hydrophobic sites that are normally buried within the native protein structure.
View Article and Find Full Text PDFProteome integrity is fundamental for cellular and organismal homeostasis. The mitochondrial unfolded protein response (UPR), a key component of the proteostasis network, is activated in a non-cell-autonomous manner in response to mitochondrial stress in distal tissues. However, the importance of inter-tissue communication for UPR inducibility under physiological conditions remains elusive.
View Article and Find Full Text PDFMany proteins self-assemble into dimers and higher-order oligomers. Therefore, the goal of this protocol is to characterize the conformational states of an endogenous protein of interest. Here, we present a protocol for assessing protein self-assembly in cell lysates using chemical cross-linking.
View Article and Find Full Text PDFChronic pain and mental health issues occur at higher rates in Veterans than the general population. One widely recognized mental health issue faced by Veterans is post-traumatic stress disorder (PTSD). Trauma symptoms and pain frequently co-occur and are mutually maintained due to shared mechanisms.
View Article and Find Full Text PDFEnrichment of periprosthetic tissue samples in blood culture bottles (BCBs) for microbiological diagnosis of periprosthetic joint infections (PJI) is more reliable than the use of an enrichment broth. Nevertheless, the extremely time-consuming homogenization of the samples for BCB processing has so far limited its use, especially in high-throughput settings. We aimed to establish a highly scalable homogenization process of tissue samples for long-term incubation in BCBs.
View Article and Find Full Text PDFAims: The majority of patients with severe aortic stenosis (AS) planned for transcatheter aortic valve implantation (TAVI) are elective outpatients. During the COVID-19 pandemic, the time between the heart team's decision and TAVI increased due to limited healthcare resources. We therefore implemented telemedical approaches to identify AS patients at risk for clinical deterioration during the waiting time.
View Article and Find Full Text PDFTrends Cell Biol
December 2024
The endoplasmic reticulum (ER) is central to the processing of luminal, transmembrane, and secretory proteins, and maintaining a functional ER is essential for organismal physiology and health. Increased protein-folding load on the ER causes ER stress, which activates quality control mechanisms to restore ER function and protein homeostasis. Beyond protein quality control, mRNA decay pathways have emerged as potent ER fidelity regulators, but their mechanistic roles in ER quality control and their interrelationships remain incompletely understood.
View Article and Find Full Text PDFThe term "dark citations," which has been previously used to refer to citations of information products outside of traditional peer-reviewed journal articles, is adapted here to refer to those that are not linked to a known indexed identifier and are effectively invisible to traditional bibliometric analysis. We investigate an unexplored source of citations in the biomedical and public health literature by surveying the extent of dark citations across the U.S.
View Article and Find Full Text PDFMost of the functions of LC3/GABARAP in macroautophagy/autophagy are considered to depend on their association with the phagophore membrane through a conjugation to a lipid. Using site-directed mutagenesis, we inhibited the conjugation of LGG-1, the single homolog of GABARAP in . Mutants that express only cytosolic forms revealed an essential role for the cleaved form of LGG-1 in autophagy but also in an autophagy-independent embryonic function.
View Article and Find Full Text PDFUbiquitin-dependent control of mitochondrial dynamics is important for protein quality and neuronal integrity. Mitofusins, mitochondrial fusion factors, can integrate cellular stress through their ubiquitylation, which is carried out by multiple E3 enzymes in response to many different stimuli. However, the molecular mechanisms that enable coordinated responses are largely unknown.
View Article and Find Full Text PDFChronic pain in Canadian Veterans is twice that of the general population and the prevalence of their related mental health concerns is alarmingly high. This likely puts their children at an increased risk of developing pain and mental health problems that can pervasively impact daily life and persist into adulthood. Pain care and military culture of (acute and chronic) pain have been identified as a top priority of Canadian Veterans.
View Article and Find Full Text PDFInsights from biomedical citation networks can be used to identify promising avenues for accelerating research and its downstream bench-to-bedside translation. Citation analysis generally assumes that each citation documents substantive knowledge transfer that informed the conception, design, or execution of the main experiments. Citations may exist for other reasons.
View Article and Find Full Text PDFThe ubiquitin-like proteins Atg8/LC3/GABARAP are required for multiple steps of autophagy, such as initiation, cargo recognition and engulfment, vesicle closure and degradation. Most of LC3/GABARAP functions are considered dependent on their post-translational modifications and their association with the autophagosome membrane through a conjugation to a lipid, the phosphatidyl-ethanolamine. Contrarily to mammals, possesses single homologs of LC3 and GABARAP families, named LGG-2 and LGG-1.
View Article and Find Full Text PDFMuscle is a highly dynamic tissue in which a variety of folding and degradation processes are active to maintain protein homeostasis (proteostasis) and functionality. The muscle-specific chaperone UNC-45 folds the motor protein myosin and assembles it into myofilaments. Malfunction of this chaperone leads to misfolding of myosin, disorganization of myofilaments, and degradation of misfolded myosin molecules by the proteasome.
View Article and Find Full Text PDFChinese cities are experiencing rapid urban development while facing severe challenges of environmental pollution. China's central government has proposed several policies to reduce urban waste. However, little is known about the adoption of these policies.
View Article and Find Full Text PDFIntroduction: Accurate measurement of health status is essential to assess veterans' needs and the effects of interventions directed at improving veterans' well-being. We conducted a systematic review to identify instruments that measure subjective health status, considering four components (ie, physical, mental, social or spiritual well-being).
Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we searched CINAHL, MEDLINE, Embase, PsycINFO, Web of Science, JSTOR, ERIC, Social Sciences Abstracts and ProQuest in June 2021 for studies reporting on the development or evaluation of instruments measuring subjective health among outpatient populations.
Mitochondria are central hubs for energy production, metabolism and cellular signal transduction in eukaryotic cells. Maintenance of mitochondrial homeostasis is important for cellular function and survival. In particular, cellular metabolic state is in constant communication with mitochondrial homeostasis.
View Article and Find Full Text PDFThe endoplasmic reticulum (ER) coordinates mRNA translation and processing of secreted and endomembrane proteins. ER-associated degradation (ERAD) prevents the accumulation of misfolded proteins in the ER, but the physiological regulation of this process remains poorly characterized. Here, in a genetic screen using an ERAD model substrate in Caenorhabditis elegans, we identified an anti-viral RNA interference pathway, referred to as ER-associated RNA silencing (ERAS), which acts together with ERAD to preserve ER homeostasis and function.
View Article and Find Full Text PDFAlternations of redox metabolism have been associated with the extension of lifespan in roundworm Caenorhabditis elegans, caused by moderate mitochondrial dysfunction, although the underlying signalling cascades are largely unknown. Previously, we identified transcriptional factor Krüppel-like factor-1 (KLF-1) as the main regulator of cytoprotective longevity-assurance pathways in the C. elegans long-lived mitochondrial mutants.
View Article and Find Full Text PDFOrganismal physiology and survival are influenced by environmental conditions and linked to protein quality control. Proteome integrity is achieved by maintaining an intricate balance between protein folding and degradation. In Caenorhabditis elegans, acute heat stress determines cell non-autonomous regulation of chaperone levels.
View Article and Find Full Text PDFBranched-chain amino acid (BCAA) metabolism is a central hub for energy production and regulation of numerous physiological processes. Controversially, both increased and decreased levels of BCAAs are associated with longevity. Using genetics and multi-omics analyses in Caenorhabditis elegans, we identified adaptive regulation of the ubiquitin-proteasome system (UPS) in response to defective BCAA catabolic reactions after the initial transamination step.
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