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1. Peroxisomal import stress activates integrated stress response and inhibits ribosome biogenesis

   https://doi.org/10.1093/pnasnexus/pgae429  

   Kim, Jinoh; Huang, Kerui; Vo, Pham_Thuy Tien; Miao, Ting; Correia, Jacinta; Kumar, Ankur; Simons, Mirre_J P; Bai, Hua (October 2024, PNAS Nexus)

   Metallo, Christian (Ed.)

   Abstract Impaired organelle-specific protein import triggers a variety of cellular stress responses, including adaptive pathways to balance protein homeostasis. Most of the previous studies focus on the cellular stress response triggered by misfolded proteins or defective protein import in the endoplasmic reticulum or mitochondria. However, little is known about the cellular stress response to impaired protein import in the peroxisome, an understudied organelle that has recently emerged as a key signaling hub for cellular and metabolic homeostasis. To uncover evolutionarily conserved cellular responses upon defective peroxisomal import, we carried out a comparative transcriptomic analysis on fruit flies with tissue-specific peroxin knockdown and human HEK293 cells expressing dominant-negative PEX5C11A. Our RNA-seq results reveal that defective peroxisomal import upregulates integrated stress response (ISR) and downregulates ribosome biogenesis in both flies and human cells. Functional analyses confirm that impaired peroxisomal import induces eIF2α phosphorylation and ATF4 expression. Loss of ATF4 exaggerates cellular damage upon peroxisomal import defects, suggesting that ATF4 activation serves as a cellular cytoprotective mechanism upon peroxisomal import stress. Intriguingly, we show that peroxisomal import stress decreases the expression of rRNA processing genes and inhibits early pre-rRNA processing, which leads to the accumulation of 47S precursor rRNA and reduction of downstream rRNA intermediates. Taken together, we identify ISR activation and ribosome biogenesis inhibition as conserved adaptive stress responses to defective peroxisomal import and uncover a novel link between peroxisomal dysfunction and rRNA processing. 

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2. Defining biological stress and stress responses based on principles of physics

   https://doi.org/10.1002/jez.2340  

   Kültz, Dietmar (January 2020, Journal of Experimental Zoology Part A: Ecological and Integrative Physiology)

   Abstract Stress represents a multi‐faceted force that is central for the evolution of life. Organisms evolve while adapting to stress and stressful contexts often represent selective bottlenecks. To understand stress effects on biological systems and corresponding coping strategies it is imperative to properly define stress and the resulting strain that triggers compensatory responses in cells and organisms. Here I am deriving such definitions for biological systems based on principles that are established in physics. The relationship between homeostasis of critical biological variables, the elastic limit, the cellular stress response (CSR), cellular homeostasis response (CHR), system dysregulation, and the breaking point (death of the system) is outlined. Dysregulation of homeostatic set‐points of biological variables perturbs the functional properties of the system, shifting them out of the evolutionarily optimized range. Such shifts are accompanied by elevated rates of macromolecular damage, which represents a nonspecific signal for induction of a universal response, the CSR. The CSR complements the CHR in re‐establishing homeostasis of the system as a whole. Moreover, the CSR is essential for coping with suboptimal conditions while the system is in a dysregulated state and for removing excessive damage that accumulates during such periods. The extreme complexity of biological systems and their emergent properties often necessitate monitoring stress effects on many biological variables simultaneously to properly deduce stress effects on the system as a whole. Therefore, increased utilization of systems biology (omics) approaches for characterizing cellular and organismal stress responses facilitates the reductionist dissection of biological stress response mechanisms. 

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3. Myosin and Alpha-actinin regulation of stress fiber contractility under tensile stress

   https://doi.org/10.1038/s41598-023-35675-7  

   Ni, Haoran; Ni, Qin; Papoian, Garegin A; Trache, Andreea; Jiang, Yi (December 2023, Scientific Reports)

   Abstract Stress fibers are actomyosin bundles that regulate cellular mechanosensation and force transduction. Interacting with the extracellular matrix through focal adhesion complexes, stress fibers are highly dynamic structures regulated by myosin motors and crosslinking proteins. Under external mechanical stimuli such as tensile forces, the stress fiber remodels its architecture to adapt to external cues, displaying properties of viscoelastic materials. How the structural remodeling of stress fibers is related to the generation of contractile force is not well understood. In this work, we simulate mechanochemical dynamics and force generation of stress fibers using the molecular simulation platform MEDYAN. We model stress fiber as two connecting bipolar bundles attached at the ends to focal adhesion complexes. The simulated stress fibers generate contractile force that is regulated by myosin motors and$$\alpha$$ $\alpha$-actinin crosslinkers. We find that stress fibers enhance contractility by reducing the distance between actin filaments to increase crosslinker binding, and this structural remodeling ability depends on the crosslinker turnover rate. Under tensile pulling force, the stress fiber shows an instantaneous increase of the contractile forces followed by a slow relaxation into a new steady state. While the new steady state contractility after pulling depends only on the overlap between actin bundles, the short-term contractility enhancement is sensitive to the tensile pulling distance. We further show that this mechanical response is also sensitive to the crosslinker turnover rate. Our results provide new insights into the stress fiber mechanics that have significant implications for understanding cellular adaptation to mechanical signaling. 

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4. Perceived stress and semen quality

   https://doi.org/10.1111/andr.13301  

   Lund, Katrine H.; Laursen, Anne Sofie; Grønborg, Therese K.; Toft, Gunnar; Jacobsen, Bjarke H.; Wang, Tanran R.; Wesselink, Amelia K.; Hatch, Elizabeth E.; Sommer, Greg J.; Eisenberg, Michael L.; et al (January 2023, Andrology)

   Abstract BackgroundPsychological stress is prevalent among reproductive‐aged men. Assessment of semen quality for epidemiological studies is challenging as data collection is expensive and cumbersome, and studies evaluating the effect of perceived stress on semen quality are inconsistent. ObjectiveTo examine the association between perceived stress and semen quality. Material and methodsWe analyzed baseline data on 644 men (1,159 semen samples) from two prospective preconception cohort studies during 2015–2021: 592 in Pregnancy Study Online (PRESTO) and 52 in SnartForaeldre.dk (SF). At study entry, men aged ≥21 years (PRESTO) and ≥18 years (SF) trying to conceive without fertility treatment completed a questionnaire on reproductive and medical history, socio‐demographics, lifestyle, and the 10‐item version of the Perceived Stress Scale (PSS; interquartile range [IQR] of scores: 0–40). After enrollment (median weeks: 2.1, IQR: 1.3–3.7), men were invited to perform in‐home semen testing, twice with 7–10 days between tests, using the Trak Male Fertility Testing System. Semen quality was characterized by semen volume, sperm concentration, and total sperm count. We fit generalized estimating equation linear regression models to estimate the percent difference in mean log‐transformed semen parameters by four PSS groups (<10, 10–14, 15–19, ≥20), adjusting for potential confounders. ResultsThe median PSS score and IQR was 15 (10–19), and 136 men (21.1%) had a PSS score ≥20. Comparing men with PSS scores ≥20 with <10, the adjusted percent difference was −2.7 (95% CI: −9.8; 5.0) for semen volume, 6.8 (95% CI: ‐10.9; 28.1) for sperm concentration, and 4.3 (95% CI: −13.8; 26.2) for total sperm count. ConclusionOur findings indicate that perceived stress is not materially associated with semen volume, sperm concentration, or total sperm count. 

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5. Residual stress and material symmetry

   https://doi.org/10.1016/j.ijengsci.2023.104013  

   Rajagopal, KR; Wineman, A (April 2024, International Journal of Engineering Science)

   There seems to be a basic misconception in several recent papers concerning the material symmetry of bodies in configurations that are pre-stressed. In this short paper we point to the source of the error and show that the material symmetry that is possible depends on the nature of the pre-stress. We also extend the results for material symmetry which have been well known within the context of simple elastic solids to the general class of simple materials. This generalization has relevance to the material symmetry of biological solids that are viscoelastic. 

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