Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense

Science, Journal Year: 2020, Volume and Issue: 370(6514)

Published: Oct. 16, 2020

Cells drop a bomb on pathogens Lipid droplets (LDs) accumulate in cells to serve as lipid storage organelles. They are also an attractive source of nutrients for many pathogens. Bosch et al. show that various proteins involved innate immunity form complexes LDs response bacterial lipopolysaccharide (see the Perspective by Green). Upon activation, became physically uncoupled from mitochondria, driving shift oxidative phosphorylation aerobic glycolysis. This work highlights ability both kill directly and establish metabolic environment conducive host defense. may inform future antimicrobial strategies age antibiotic resistance. Science , this issue p. eaay8085 ; see 294

Language: Английский

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Targeting Mitochondria-Located circRNA SCAR Alleviates NASH via Reducing mROS Output

Cell, Journal Year: 2020, Volume and Issue: 183(1), P. 76 - 93.e22

Published: Sept. 14, 2020

Language: Английский

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The role of mitochondria in aging

Journal of Clinical Investigation, Journal Year: 2018, Volume and Issue: 128(9), P. 3662 - 3670

Published: July 29, 2018

The biological basis of human aging remains one the greatest unanswered scientific questions. Increasing evidence, however, points to a role for alterations in mitochondrial function as potential central regulator process. Here, we focus primarily on three aspects biology that link this ancient organelle how and why age. In particular, discuss mitochondria regulating innate immune system, mechanisms linking quality control age-dependent pathology, possibility mitochondrial-to-nuclear signaling might regulate rate aging.

Language: Английский

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PINK1/PARKIN signalling in neurodegeneration and neuroinflammation

Acta Neuropathologica Communications, Journal Year: 2020, Volume and Issue: 8(1)

Published: Nov. 9, 2020

Abstract Mutations in the PTEN-induced kinase 1 (PINK1) and Parkin RBR E3 ubiquitin-protein ligase (PARKIN) genes are associated with familial forms of Parkinson’s disease (PD). PINK1, a protein kinase, PARKIN, an ubiquitin ligase, control specific elimination dysfunctional or superfluous mitochondria, thus fine-tuning mitochondrial network preserving energy metabolism. PINK1 regulates PARKIN translocation impaired mitochondria drives their removal via selective autophagy, process known as mitophagy. As knowledge obtained using different transgenic animal models is being gathered, growing evidence supports contribution mitophagy impairment to several human pathologies, including PD Alzheimer’s diseases (AD). Therefore, therapeutic interventions aiming modulate PINK1/PARKIN signalling might have potential treat these diseases. In this review, we will start by discussing how interplay helps mediate physiology. We continue debating role dysfunction disorders such amyotrophic lateral sclerosis, Alzheimer’s, Huntington’s diseases, well eye age-related macular degeneration glaucoma, causative factors leading PINK1/PARKIN-mediated neurodegeneration neuroinflammation. Finally, discuss gene augmentation possibilities particular focus on AD, glaucoma.

Language: Английский

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Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease

Immunity, Journal Year: 2021, Volume and Issue: 54(6), P. 1257 - 1275.e8

Published: May 16, 2021

The kinetics of the immune changes in COVID-19 across severity groups have not been rigorously assessed. Using immunophenotyping, RNA sequencing, and serum cytokine analysis, we analyzed serial samples from 207 SARS-CoV2-infected individuals with a range disease severities over 12 weeks symptom onset. An early robust bystander CD8+ T cell response, without systemic inflammation, characterized asymptomatic or mild disease. Hospitalized had delayed responses inflammation that was already evident near onset, indicating immunopathology may be inevitable some individuals. Viral load did correlate this pathological response but subsequent severity. Immune recovery is complex, profound persistent cellular abnormalities severe correlating altered inflammatory responses, signatures associated increased oxidative phosphorylation replacing those driven by cytokines tumor necrosis factor (TNF) interleukin (IL)-6. These late immunometabolic defects clinical implications.

Language: Английский

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