bims-cemest Biomed News
on Cell metabolism and stress
Issue of 2024–12–22
seven papers selected by
Jessica Rosarda, Uniformed Services University
  1. In-Gel Activity Assay of Mammalian Mitochondrial and Cytosolic Aconitases, Surrogate Markers of Compartment-Specific Oxidative Stress and Iron Status.
  2. Impact of Physical Activity on Cellular Metabolism Across Both Neurodegenerative and General Neurological Conditions: A Narrative Review.
  3. Magnesium Supplementation Modifies Arthritis Synovial and Splenic Transcriptomic Signatures Including Ferroptosis and Cell Senescence Biological Pathways.
  4. NAD+ Boosting Strategies.
  5. Emerging role of IRE1α in vascular diseases.
  6. Progress in Lactate Metabolism and Its Regulation via Small Molecule Drugs.
  7. A model of inborn metabolism errors associated with adenine amyloid-like fiber formation reduces TDP-43 aggregation and toxicity in yeast.
  1. Bio Protoc. 2024 Dec 05. 14(23): e5126
    In-Gel Activity Assay of Mammalian Mitochondrial and Cytosolic Aconitases, Surrogate Markers of Compartment-Specific Oxidative Stress and Iron Status.
    Wing-Hang Tong, Tracey A Rouault.
      Two aconitase isoforms are present in mammalian cells: the mitochondrial aconitase (ACO2) that catalyzes the reversible isomerization of citrate to isocitrate in the citric acid cycle, and the bifunctional cytosolic enzyme (ACO1), which also plays a role as an RNA-binding protein in the regulation of intracellular iron metabolism. Aconitase activities in the different subcellular compartments can be selectively inactivated by different genetic defects, iron depletion, and oxidative or nitrative stress. Aconitase contains a [4Fe-4S]2+ cluster that is essential for substrate coordination and catalysis. Many Fe-S clusters are sensitive to oxidative stress, nitrative stress, and reduced iron availability, which forms the basis of redox- and iron-mediated regulation of intermediary metabolism via aconitase and other Fe-S cluster-containing metabolic enzymes, such as succinate dehydrogenase. As such, ACO1 and ACO2 activities can serve as compartment-specific surrogate markers of oxygen levels, reactive oxygen species (ROS), reactive nitrogen species (RNS), iron bioavailability, and the status of intermediary and iron metabolism. Here, we provide a protocol describing a non-denaturing polyacrylamide gel electrophoresis (PAGE)-based procedure that has been successfully used to monitor ACO1 and ACO2 aconitase activities simultaneously in human and mouse cells and tissues. Key features • Monitoring aconitase activity changes in the mitochondria and cytosol simultaneously in response to oxidative or nitrative stress, iron depletion, and various pathophysiological conditions. • Optimized for human and mouse cell lines and tissue samples. • Semi-quantitative detection of aconitase isoforms with different states of phosphorylation and/or post-translational modification.
    Keywords:  ACO1; ACO2; Aconitase; IRE-BP1; IRP1; Iron metabolism; Iron regulatory protein 1; Iron response element binding protein 1; Nitrative stress; Oxidative stress
    DOI:  https://doi.org/10.21769/BioProtoc.5126
  2. Cells. 2024 Nov 22. pii: 1940. [Epub ahead of print]13(23):
    Impact of Physical Activity on Cellular Metabolism Across Both Neurodegenerative and General Neurological Conditions: A Narrative Review.
    Vicente Javier Clemente-Suárez, Alejandro Rubio-Zarapuz, Pedro Belinchón-deMiguel, Ana Isabel Beltrán-Velasco, Alexandra Martín-Rodríguez, José Francisco Tornero-Aguilera.
       BACKGROUND: Regular physical activity plays a crucial role in modulating cellular metabolism and mitigating the progression of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Multiple Sclerosis.
    OBJECTIVE: The objective of this review is to evaluate the molecular mechanisms by which exercise influences cellular metabolism, with a focus on its potential as a therapeutic intervention for neurological disorders.
    METHODS: A comprehensive literature review was conducted using peer-reviewed scientific articles, with a focus on the period between 2015 and 2024, to analyze the effects of exercise on mitochondrial function, oxidative stress, and metabolic health.
    RESULTS: The findings indicate that exercise promotes mitochondrial biogenesis, enhances oxidative phosphorylation, and reduces reactive oxygen species, contributing to improved energy production and cellular resilience. These metabolic adaptations are associated with delayed disease progression and reduced symptoms in patients with neurodegenerative conditions. Additionally, integrating exercise with nutritional strategies may further enhance therapeutic outcomes by addressing metabolic disturbances comprehensively.
    CONCLUSIONS: This review concludes that personalized exercise protocols should be developed to optimize metabolic benefits for patients with neurological diseases, while future research should focus on biomarker development for individualized treatment approaches. These findings highlight the importance of non-pharmacological interventions in managing neurodegenerative diseases.
    Keywords:  cellular metabolism; exercise therapy; mitochondrial dysfunction; neurodegenerative diseases; physical activity
    DOI:  https://doi.org/10.3390/cells13231940
  3. Nutrients. 2024 Dec 09. pii: 4247. [Epub ahead of print]16(23):
    Magnesium Supplementation Modifies Arthritis Synovial and Splenic Transcriptomic Signatures Including Ferroptosis and Cell Senescence Biological Pathways.
    Teresina Laragione, Carolyn Harris, Pércio S Gulko.
       BACKGROUND: Rheumatoid arthritis (RA) is a common systemic autoimmune inflammatory disease that can cause joint damage. We have recently reported that oral magnesium supplementation significantly reduces disease severity and joint damage in models of RA.
    METHODS: In the present study, we analyzed the transcriptome of spleens and synovial tissues obtained from mice with KRN serum-induced arthritis (KSIA) consuming either a high Mg supplemented diet (Mg2800; n = 7) or a normal diet (Mg500; n = 7). Tissues were collected at the end of a 15-day KSIA experiment. RNA was extracted and used for sequencing and analyses.
    RESULTS: There was an enrichment of differentially expressed genes (DEGs) belonging to Reactome and Gene Ontology (GO) pathways implicated in RA pathogenesis such as RHO GTPases, the RUNX1 pathway, oxidative stress-induced senescence, and the senescence-associated secretory phenotype. Actc1 and Nr4a3 were among the genes with the highest expression, while Krt79 and Ffar2 were among the genes with the lowest expression in synovial tissues of the Mg2800 group compared with the Mg500 group. Spleens had an enrichment for the metabolism of folate and pterines and the HSP90 chaperone cycle for the steroid hormone receptor.
    CONCLUSIONS: We describe the tissue transcriptomic consequences of arthritis-protecting Mg supplementation in KSIA mice. These results show that oral Mg supplementation may interfere with the response to oxidative stress and senescence and other processes known to participate in RA pathogenesis. We provide new evidence supporting the disease-suppressing effect of increased Mg intake in arthritis and its potential to become a new addition to the therapeutic options for RA and other autoimmune and inflammatory diseases.
    Keywords:  arthritis; autoimmune; diet; inflammation; senescence
    DOI:  https://doi.org/10.3390/nu16234247
  4. Subcell Biochem. 2024 ;107 63-90
    NAD+ Boosting Strategies.
    Jared Rice, Sofie Lautrup, Evandro F Fang.
      Nicotinamide adenine dinucleotide (oxidized form, NAD+) serves as a co-substrate and co-enzyme in cells to execute its key roles in cell signalling pathways and energetic metabolism, arbitrating cell survival and death. It was discovered in 1906 by Arthur Harden and William John Young in yeast extract which could accelerate alcohol fermentation. NAD acts as an electron acceptor and cofactor throughout the processes of glycolysis, Tricarboxylic Acid Cycle (TCA), β oxidation, and oxidative phosphorylation (OXPHOS). NAD has two forms: NAD+ and NADH. NAD+ is the oxidising coenzyme that is reduced when it picks up electrons. NAD+ levels steadily decline with age, resulting in an increase in vulnerability to chronic illness and perturbed cellular metabolism. Boosting NAD+ levels in various model organisms have resulted in improvements in healthspan and lifespan extension. These results have prompted a search for means by which NAD+ levels in the body can be augmented by both internal and external means. The aim of this chapter is to provide an overview of NAD+, appraise clinical evidence of its importance and success in potentially extending health- and lifespan, as well as to explore NAD+ boosting strategies.
    Keywords:  Ageing; Caloric restriction; NAD+; Neurodegeneration; Nicotinamide mononucleotide; Nicotinamide riboside; Oxidative stress; Supplementation
    DOI:  https://doi.org/10.1007/978-3-031-66768-8_4
  5. J Cell Commun Signal. 2024 Dec;18(4): e12056
    Emerging role of IRE1α in vascular diseases.
    Jia Shi, Fan He, Xiaogang Du.
      A mounting body of evidence suggests that the endoplasmic reticulum stress and the unfolded protein response are involved in the underlying mechanisms responsible for vascular diseases. Inositol-requiring protein 1α (IRE1α), the most ancient branch among the UPR-related signaling pathways, can possess both serine/threonine kinase and endoribonuclease (RNase) activity and can perform physiological and pathological functions. The IRE1α-signaling pathway plays a critical role in the pathology of various vascular diseases. In this review, we provide a general overview of the physiological function of IRE1α and its pathophysiological role in vascular diseases.
    Keywords:  IRE1α; XBP1; atherosclerosis; vascular disease
    DOI:  https://doi.org/10.1002/ccs3.12056
  6. Molecules. 2024 Nov 29. pii: 5656. [Epub ahead of print]29(23):
    Progress in Lactate Metabolism and Its Regulation via Small Molecule Drugs.
    Jin Liu, Feng Zhou, Yang Tang, Linghui Li, Ling Li.
      Lactate, once viewed as a byproduct of glycolysis and a metabolic "waste", is now recognized as an energy-providing substrate and a signaling molecule that modulates cellular functions under pathological conditions. The discovery of histone lactylation in 2019 marked a paradigm shift, with subsequent studies revealing that lactate can undergo lactylation with both histone and non-histone proteins, implicating it in the pathogenesis of various diseases, including cancer, liver fibrosis, sepsis, ischemic stroke, and acute kidney injury. Aberrant lactate metabolism is associated with disease onset, and its levels can predict disease outcomes. Targeting lactate production, transport, and lactylation may offer therapeutic potential for multiple diseases, yet a systematic summary of the small molecules modulating lactate and its metabolism in various diseases is lacking. This review outlines the sources and clearance of lactate, as well as its roles in cancer, liver fibrosis, sepsis, ischemic stroke, myocardial infarction, and acute kidney injury, and summarizes the effects of small molecules on lactate regulation. It aims to provide a reference and direction for future research.
    Keywords:  glycolysis; lactate; physiology and diseases; small molecule drugs
    DOI:  https://doi.org/10.3390/molecules29235656
  7. bioRxiv. 2024 Dec 07. pii: 2024.12.03.626668. [Epub ahead of print]
    A model of inborn metabolism errors associated with adenine amyloid-like fiber formation reduces TDP-43 aggregation and toxicity in yeast.
    Sangeun Park, Sei-Kyoung Park, Susan W Liebman.
      TDP-43 is linked to human diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). Expression of TDP-43 in yeast is known to be toxic, cause cells to elongate, form liquid-like aggregates, and inhibit autophagy and TOROID formation. Here, we used the apt1Δ aah1Δ yeast model of disorders of inborn errors of metabolism, previously shown to lead to intracellular adenine accumulation and adenine amyloid-like fiber formation, to explore interactions with TDP-43. Results show that the double deletion shifts the TDP-43 aggregates from a liquid-like, toward a more amyloid-like, state. At the same time the deletions reduce TDP-43's effects on toxicity, cell morphology, autophagy, and TOROID formation without affecting the level of TDP-43. This suggests that the liquid-like and not amyloid-like TDP-43 aggregates are responsible for the deleterious effects in yeast. How the apt1Δ aah1Δ deletions alter TDP-43 aggregate formation is not clear. Possibly, it results from adenine/TDP-43 fiber interactions as seen for other heterologous fibers. The work offers new insights into the potential interactions between metabolite-based amyloids and pathological protein aggregates, with broad implications for understanding protein misfolding diseases.
    DOI:  https://doi.org/10.1101/2024.12.03.626668
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