Peroxisomes in host defense

Cara, Francesca Di

doi:10.1371/journal.ppat.1008636

Cited by 24 publications

(18 citation statements)

References 69 publications

(83 reference statements)

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“…There is substantial evidence that peroxisomes actively contribute to cell signaling and that their function is required for human health ( Beach et al, 2012 ; Braverman et al, 2013 ; Braverman et al, 2013 ; Fransen et al, 2013 ; Trompier et al, 2014 ; Colasante et al, 2015 ). Recent evidence corroborated a role for peroxisomes in modulating immune responses ( Dixit et al, 2010 ; Di Cara et al, 2017 ; Di Cara, 2020 ). Indeed, peroxisomes were first described to have an important role during viral infections serving as signal platforms for mitochondrial antiviral signaling (MAVS) proteins and induction of interferon responses ( Sychev et al, 2017 ; Xu et al, 2017 ; Cook et al, 2019 ; Merkling et al, 2019 ).…”

Section: Introductionmentioning

confidence: 79%

“…Peroxisomes are highly conserved organelles and play a pivotal role in lipid metabolism and ROS such as hydrogen peroxide (H 2 O 2 ) catabolism ( Liu et al, 2019 ). Both ROS and lipids are important mediators in cellular signaling in immune cells ( Di Cara, 2020 ; Di Cara et al, 2017 ; 2019 ). H 2 O 2 is a permeable and diffusible molecule involved in inter- and intracellular signaling during host defense ( Bedard and Krause, 2007 ; Blander and Sander, 2012 ).…”

Section: Resultsmentioning

confidence: 99%

“…The present study aimed to define the role of peroxisome metabolism in the context of TLR and IgE-mediated activation of MCs. In the immune compartment, peroxisome-derived lipids have been shown to be involved in the development, survival and functions of multiple innate and adaptive immune effector cells ( Brutkiewicz and Dent, 2012 ; Facciotti et al, 2012 ; Di Cara, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

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Peroxisomes Regulate Cellular Free Fatty Acids to Modulate Mast Cell TLR2, TLR4, and IgE-Mediated Activation

Meghnem

Leong

Pinelli

et al. 2022

Front. Cell Dev. Biol.

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Mast cells are specialized, tissue resident, immune effector cells able to respond to a wide range of stimuli. MCs are involved in the regulation of a variety of physiological functions, including vasodilation, angiogenesis and pathogen elimination. In addition, MCs recruit and regulate the functions of many immune cells such as dendritic cells, macrophages, T cells, B cells and eosinophils through their selective production of multiple cytokines and chemokines. MCs generate and release multi-potent molecules, such as histamine, proteases, prostanoids, leukotrienes, heparin, and many cytokines, chemokines, and growth factors through both degranulation dependent and independent pathways. Recent studies suggested that metabolic shifts dictate the activation and granule content secretion by MCs, however the metabolic signaling promoting these events is at its infancy. Lipid metabolism is recognized as a pivotal immunometabolic regulator during immune cell activation. Peroxisomes are organelles found across all eukaryotes, with a pivotal role in lipid metabolism and the detoxification of reactive oxygen species. Peroxisomes are one of the emerging axes in immunometabolism. Here we identified the peroxisome as an essential player in MCs activation. We determined that lack of functional peroxisomes in murine MCs causes a significant reduction of interleukin-6, Tumor necrosis factor and InterleukinL-13 following immunoglobulin IgE-mediated and Toll like receptor 2 and 4 activation compared to the Wild type (WT) BMMCs. We linked these defects in cytokine release to defects in free fatty acids homeostasis. In conclusion, our study identified the importance of peroxisomal fatty acids homeostasis in regulating mast cell-mediated immune functions.

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Section: Introductionmentioning

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Peroxisomes Regulate Cellular Free Fatty Acids to Modulate Mast Cell TLR2, TLR4, and IgE-Mediated Activation

Meghnem

Leong

Pinelli

et al. 2022

Front. Cell Dev. Biol.

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“…Furthermore, peroxisomes play an important role in the development of the brain and their dysfunction may contribute to neurological pathologies including amyotrophic lateral sclerosis and Alzheimer's disease (Berger et al, 2016). More recent evidence supports a major function of peroxisomes in regulating the response of the immune system to pathogenic attack in several animals (Odendall et al, 2014;Di Cara et al, 2017;Di Cara, 2020). Plant peroxisomes are critical for oil mobilization during early seedling development and play a role in the metabolism of the toxic by-product 2phosphoglycolate derived from an O 2 -consuming side reaction of RuBisCO.…”

Section: Peroxisome Functionsmentioning

confidence: 99%

Sharing the wealth: The versatility of proteins targeted to peroxisomes and other organelles

Bittner

Stehlik

Freitag

2022

Front. Cell Dev. Biol.

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Peroxisomes are eukaryotic organelles with critical functions in cellular energy and lipid metabolism. Depending on the organism, cell type, and developmental stage, they are involved in numerous other metabolic and regulatory pathways. Many peroxisomal functions require factors also relevant to other cellular compartments. Here, we review proteins shared by peroxisomes and at least one different site within the cell. We discuss the mechanisms to achieve dual targeting, their regulation, and functional consequences. Characterization of dual targeting is fundamental to understand how peroxisomes are integrated into the metabolic and regulatory circuits of eukaryotic cells.

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“…Peroxisomes play a crucial role in the regulation of reactive oxygen species (ROS) production and the catabolism of long-chain fatty acids [ 8 , 9 ]. These functions of peroxisomes are well studied in eukaryotes, plants, and fungi; however, their role in bacterial infection, specifically during mycobacterial infection, is poorly understood [ 10 , 11 , 12 ]. A study by Karnati et al demonstrated the presence of peroxisomes in all cell types of the human lung, with heterogeneity in their structure, numerical abundance, and enzyme composition depending on the metabolic needs of the equivalent cell types [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Mycobacterium tuberculosis Acetyltransferase Suppresses Oxidative Stress by Inducing Peroxisome Formation in Macrophages

Behera

Jain

Ganguli

et al. 2022

IJMS

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Mycobacterium tuberculosis (Mtb) inhibits host oxidative stress responses facilitating its survival in macrophages; however, the underlying molecular mechanisms are poorly understood. Here, we identified a Mtb acetyltransferase (Rv3034c) as a novel counter actor of macrophage oxidative stress responses by inducing peroxisome formation. An inducible Rv3034c deletion mutant of Mtb failed to induce peroxisome biogenesis, expression of the peroxisomal β-oxidation pathway intermediates (ACOX1, ACAA1, MFP2) in macrophages, resulting in reduced intracellular survival compared to the parental strain. This reduced virulence phenotype was rescued by repletion of Rv3034c. Peroxisome induction depended on the interaction between Rv3034c and the macrophage mannose receptor (MR). Interaction between Rv3034c and MR induced expression of the peroxisomal biogenesis proteins PEX5p, PEX13p, PEX14p, PEX11β, PEX19p, the peroxisomal membrane lipid transporter ABCD3, and catalase. Expression of PEX14p and ABCD3 was also enhanced in lungs from Mtb aerosol-infected mice. This is the first report that peroxisome-mediated control of ROS balance is essential for innate immune responses to Mtb but can be counteracted by the mycobacterial acetyltransferase Rv3034c. Thus, peroxisomes represent interesting targets for host-directed therapeutics to tuberculosis.

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Peroxisomes in host defense

Cited by 24 publications

References 69 publications

Peroxisomes Regulate Cellular Free Fatty Acids to Modulate Mast Cell TLR2, TLR4, and IgE-Mediated Activation

Peroxisomes Regulate Cellular Free Fatty Acids to Modulate Mast Cell TLR2, TLR4, and IgE-Mediated Activation

Sharing the wealth: The versatility of proteins targeted to peroxisomes and other organelles

Mycobacterium tuberculosis Acetyltransferase Suppresses Oxidative Stress by Inducing Peroxisome Formation in Macrophages

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