Mitochondrial metabolism regulates macrophage biology

Wang, Yafang; Li, Na; Zhang, Xin; Horng, Tiffany

doi:10.1016/j.jbc.2021.100904

Cited by 133 publications

(110 citation statements)

References 117 publications

(112 reference statements)

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“…IRG1 was found as the most upregulated protein detected by both CAT-Prox and immunoblotting, indicating the high fidelity of CAT-Proxbased proteomics (Figure 3g). Noteworthy, Aco2 (aconitase 2) and IRG1 (aconitate decarboxylase 1) were responsible for itaconate production in a tandem manner, 28 agreeing with the previous discovery of enhanced itaconate production in LPSstimulated macrophages. 29,30 Similarly, the increase of reactive electrophile species 29,30 was likely due to the upregulation of Acadsb.…”

Section: ■ Results and Discussionsupporting

confidence: 91%

Bioorthogonal Photocatalytic Decaging-Enabled Mitochondrial Proteomics

et al. 2021

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Spatiotemporally resolved dissection of subcellular proteome is crucial to our understanding of cellular functions in health and disease. We herein report a bioorthogonal and photocatalytic decaging-enabled proximity labeling strategy (CAT-Prox) for spatiotemporally resolved mitochondrial proteome profiling in living cells. Our systematic survey of the photocatalysts has led to the identification of Ir(ppy)2bpy as a bioorthogonal and mitochondria-targeting catalyst that allowed photocontrolled, rapid rescue of azidobenzyl-caged quinone methide as a highly reactive Michael acceptor for proximity-based protein labeling in mitochondria of live cells. Upon careful validation through in vitro labeling, mitochondria-targeting specificity, in situ catalytic activity as well as protein tagging, we applied CAT-Prox for mitochondria proteome profiling in living Hela cells as well as hard-to-transfect macrophage RAW264.7 cells with approximately 70% mitochondria specificity observed from up to 300 proteins enriched. Finally, CAT-Prox was further applied to the dynamic dissection of mitochondria proteome of macrophage cells upon lipopolysaccharide stimulation. By integrating photocatalytic decaging chemistry with proximity-based protein labeling, CAT-Prox offers a general, catalytic, and nongenetic alternative to the enzyme-based proximity labeling strategies for diverse live cell settings.

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Section: ■ Results and Discussionsupporting

confidence: 91%

Bioorthogonal Photocatalytic Decaging-Enabled Mitochondrial Proteomics

et al. 2021

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“…Mitochondria are also key for energy metabolism in macrophages and the regulation of macrophage biology [ 55 , 56 ]. For instance, M1-like macrophages are characterized by increased glycolytic metabolism, production of pro-inflammatory mediators (e.g., ROS, IL-6), and mitochondria fragmentation (fission), while M2-like macrophages display increased FAO and release of anti-inflammatory cytokines, as well as mitochondria elongation/fusion [ 57 ].…”

Section: Resultsmentioning

confidence: 99%

Asymptomatic Hyperuricemia Promotes Recovery from Ischemic Organ Injury by Modulating the Phenotype of Macrophages

Gnemmi

et al. 2022

Cells

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Acute organ injury, such as acute kidney injury (AKI) and disease (AKD), are major causes of morbidity and mortality worldwide. Hyperuricemia (HU) is common in patients with impaired kidney function but the impact of asymptomatic HU on the different phases of AKI/AKD is incompletely understood. We hypothesized that asymptomatic HU would attenuate AKD because soluble, in contrast to crystalline, uric acid (sUA) can attenuate sterile inflammation. In vitro, 10 mg/dL sUA decreased reactive oxygen species and interleukin-6 production in macrophages, while enhancing fatty acid oxidation as compared with a physiological concentration of 5 mg/dL sUA or medium. In transgenic mice, asymptomatic HU of 7–10 mg/dL did not affect post-ischemic AKI/AKD but accelerated the recovery of kidney excretory function on day 14. Improved functional outcome was associated with better tubular integrity, less peritubular inflammation, and interstitial fibrosis. Mechanistic studies suggested that HU shifted macrophage polarization towards an anti-inflammatory M2-like phenotype characterized by expression of anti-oxidative and metabolic genes as compared with post-ischemic AKI-chronic kidney disease transition in mice without HU. Our data imply that asymptomatic HU acts as anti-oxidant on macrophages and tubular epithelial cells, which endorses the recovery of kidney function and structure upon AKI.

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“…The changes of mitochondrial dynamics between fusion and fission play an important role in macrophage function [ 40 , 41 ] and previous studies demonstrated that DRP1-dependent mitochondrial fission could induce the pro-inflammatory activation of macrophages [ 20 ]. In this study, mitochondrial fission and the pro-inflammatory response induced by STING activation were all inhibited by transfection of DRP1 shRNA in LPS-treated KCs, indicating that DRP1-mediated mitochondrial fission was required for STING signaling activation.…”

Section: Discussionmentioning

confidence: 99%