STING-mediated inflammation in Kupffer cells contributes to progression of nonalcoholic steatohepatitis

Journal of Clinical Investigation, Journal Year: 2018, Volume and Issue: 129(2), P. 546 - 555

Published: Dec. 17, 2018

Innate immune activation contributes to the transition from nonalcoholic fatty liver steatohepatitis (NASH). Stimulator of IFN genes (STING, also referred Tmem173) is a universal receptor that recognizes released DNA and triggers innate activation. In this work, we investigated role STING in progression NASH mice. Both methionine- choline-deficient diet (MCD) high-fat (HFD) were used induce Strikingly, deficiency attenuated steatosis, fibrosis, inflammation livers both murine models NASH. Additionally, increased fasting glucose levels mice independently insulin, but mitigated HFD-induced insulin resistance weight gain reduced cholesterol, triglycerides, LDL serum; it enhanced HDL. The mitochondrial (mtDNA) hepatocytes HFD-fed induced TNF-α IL-6 expression cultured Kupffer cells (KCs), which was by or pretreatment with BAY11-7082 (an NF-κB inhibitor). Finally, chronic exposure 5,6-dimethylxanthenone-4-acetic acid (DMXAA, agonist) led hepatic steatosis WT mice, not STING-deficient We proposed functions as an mtDNA sensor KCs under lipid overload induces NF-κB-dependent

Language: Английский

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Mitochondria as Signaling Organelles Control Mammalian Stem Cell Fate

Cell stem cell, Journal Year: 2021, Volume and Issue: 28(3), P. 394 - 408

Published: March 1, 2021

Language: Английский

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Mitochondria in health, disease, and aging

Physiological Reviews, Journal Year: 2023, Volume and Issue: 103(4), P. 2349 - 2422

Published: April 6, 2023

Mitochondria are well known as organelles responsible for the maintenance of cellular bioenergetics through production ATP. Although oxidative phosphorylation may be their most important function, mitochondria also integral synthesis metabolic precursors, calcium regulation, reactive oxygen species, immune signaling, and apoptosis. Considering breadth responsibilities, fundamental metabolism homeostasis. Appreciating this significance, translational medicine has begun to investigate how mitochondrial dysfunction can represent a harbinger disease. In review, we provide detailed overview metabolism, bioenergetics, dynamics, autophagy, damage-associated molecular patterns, mitochondria-mediated cell death pathways, at any these levels is associated with disease pathogenesis. Mitochondria-dependent pathways thereby an attractive therapeutic target ameliorating human

Language: Английский

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Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact

Cell, Journal Year: 2020, Volume and Issue: 183(5), P. 1185 - 1201.e20

Published: Nov. 1, 2020

Language: Английский

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The mitochondrial transcription factor TFAM in neurodegeneration: emerging evidence and mechanisms

FEBS Letters, Journal Year: 2018, Volume and Issue: 592(5), P. 793 - 811

Published: Jan. 24, 2018

The mitochondrial transcription factor A, or TFAM , is a DNA (mt )‐binding protein essential for genome maintenance. functions in determining the abundance of by regulating packaging, stability, and replication. More recently, has been shown to play central role mt stress‐mediated inflammatory response. Emerging evidence indicates that decreased copy number associated with several aging‐related pathologies; however, little known about association disease. In this Review, we evaluate potential associations altered levels neurodegeneration. We also describe mechanisms which replication, initiation, ‐mediated endogenous danger signals may impact homeostasis Alzheimer, Huntington, Parkinson, other neurodegenerative diseases.

Language: Английский

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