Cellular adaptation to hypoxia through hypoxia inducible factors and beyond

Nature Reviews Molecular Cell Biology, Journal Year: 2020, Volume and Issue: 21(5), P. 268 - 283

Published: March 6, 2020

Language: Английский

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The assembly, regulation and function of the mitochondrial respiratory chain

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 23(2), P. 141 - 161

Published: Oct. 7, 2021

Language: Английский

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Therapeutic targeting of the hypoxic tumour microenvironment

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 18(12), P. 751 - 772

Published: July 29, 2021

Language: Английский

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Reactive Oxygen Species in Macrophages: Sources and Targets

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Sept. 30, 2021

Reactive oxygen species (ROS) are fundamental for macrophages to eliminate invasive microorganisms. However, as observed in nonphagocytic cells, ROS play essential roles processes that different from pathogen killing, signal transduction, differentiation, and gene expression. The outcomes of these events likely depend on the specific subcellular site formation, well duration extent production. While excessive accumulation has long been appreciated its detrimental effects, there is now a deeper understanding their signaling molecules. This could explain failure "all or none" pharmacologic approach with global antioxidants treat several diseases. NADPH oxidase first source identified macrophages. growing evidence highlights mitochondria crucial formation mainly due electron leakage respiratory chain enzymes, such monoamine oxidases. Their role redox signaling, together exact only partially elucidated. Hence, it identify intracellular sources how they influence cellular both physiological pathological conditions develop therapies targeting oxidative networks. In this review, we will focus sites impact metabolic inflammatory highlighting mitochondrial compared non-mitochondrial sources.

Language: Английский

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The NLRP3 inflammasome inhibitor OLT1177 rescues cognitive impairment in a mouse model of Alzheimer’s disease

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(50), P. 32145 - 32154

Published: Nov. 30, 2020

Numerous studies demonstrate that neuroinflammation is a key player in the progression of Alzheimer's disease (AD). Interleukin (IL)-1β main inducer inflammation and therefore prime target for therapeutic options. The inactive IL-1β precursor requires processing by nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome into mature active form. Studies have shown up-regulated brains patients with AD, genetic inactivation NLRP3 improves behavioral tests synaptic plasticity phenotypes murine model disease. In present study, we analyzed effect pharmacological inhibition using dapansutrile (OLT1177), an oral NLRP3-specific inhibitor safe humans. Six-month-old WT APP/PS1 mice were fed standard mouse chow or OLT1177-enriched mo. Morris water maze test revealed impaired learning memory ability 9-mo-old (P = 0.001), which was completely rescued OLT1177 to 0.008 untreated APP/PS1). Furthermore, our findings mo diet can rescue this AD 0.007 addition, microglia less activated 0.07) number plaques reduced cortex 0.03) following administration. We also observed dose-dependent normalization plasma metabolic markers those mice. This study suggests potential treating inflammasome.

Language: Английский

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Itaconate and itaconate derivatives target JAK1 to suppress alternative activation of macrophages

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(3), P. 487 - 501.e8

Published: March 1, 2022

Language: Английский

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Compartmentalised acyl-CoA metabolism and roles in chromatin regulation

Molecular Metabolism, Journal Year: 2020, Volume and Issue: 38, P. 100941 - 100941

Published: Feb. 14, 2020

Many metabolites serve as important signalling molecules to adjust cellular activities and functions based on nutrient availability. Links between acetyl-CoA metabolism, histone lysine acetylation, gene expression have been documented studied over the past decade. In recent years, several additional acyl modifications residues identified, which depend acyl-coenzyme A thioesters (acyl-CoAs) donors. Acyl-CoAs are intermediates of multiple distinct metabolic pathways, substantial evidence has emerged that acylation is metabolically sensitive. Nevertheless, sources acyl-CoAs used for chromatin modification in most cases remain poorly understood. Elucidating how these diverse chemical coupled regulated by metabolism deciphering their functional significance. this article, we review pathways produce acyl-CoAs, well emerging roles regulation. Because extensively reviewed elsewhere, will focus four other acyl-CoA integral major also known modify histones: succinyl-CoA, propionyl-CoA, crotonoyl-CoA, butyryl-CoA. We briefly mention species, present opportunities further research; malonyl-CoA, glutaryl-CoA, 3-hydroxybutyryl-CoA, 2-hydroxyisobutyryl-CoA, lactyl-CoA. Each species indicating potential report shifts status cell. For each metabolite, consider it participates from derived, compartmentalisation its factors reported influence abundance nuclear highlight biological metabolically-linked marks. Finally, aim illuminate key questions they relate control modification. majority annotated mitochondrial processes. Since not be directly transported across membranes, must synthesized outside mitochondria potentially within nucleus participate Thus, subcellular likely plays a role regulation acylation. Metabolite tracing combination with targeting relevant enzymes transporters help map connect The specific function may determined part biochemical properties affect propensity enzymatic versus non-enzymatic protein modification, various can add, remove bind Further, competitive inhibitory effects different make determining relative contexts understand An improved more nuanced understanding physiological disease-related processes emerge answered.

Language: Английский

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Cellular senescence: all roads lead to mitochondria

FEBS Journal, Journal Year: 2022, Volume and Issue: 290(5), P. 1186 - 1202

Published: Jan. 20, 2022

Senescence is a multi-functional cell fate, characterized by an irreversible cell-cycle arrest and pro-inflammatory phenotype, commonly known as the senescence-associated secretory phenotype (SASP). Emerging evidence indicates that accumulation of senescent cells in multiple tissues drives tissue dysfunction several age-related conditions. This has spurred academic community industry to identify new therapeutic interventions targeting this process. Mitochondrial often-unappreciated hallmark cellular senescence which plays important roles not only growth but also development SASP resistance cell-death. Here, we review supports role for mitochondria describe underlying mechanisms. Finally, propose detailed road map mitochondrial biology will be crucial guide future senotherapies.

Language: Английский

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Metabolic orchestration of the wound healing response

Cell Metabolism, Journal Year: 2021, Volume and Issue: 33(9), P. 1726 - 1743

Published: Aug. 11, 2021

Language: Английский

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The Immunomodulatory Potential of the Metabolite Itaconate

Trends in Immunology, Journal Year: 2019, Volume and Issue: 40(8), P. 687 - 698

Published: June 6, 2019

Language: Английский

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