Elsevier

Redox Biology

Review Article

Reactive oxygen species and mitochondria: A nexus of cellular homeostasis

Under a Creative Commons license

Open access

Highlights

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Mitochondrial ROS production is regulated by and incorporated into amnesty pathways.

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ROS regulate mitophagy and xenophagy and neutrophil extracellular trap formation.

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Mitochondria and mitochondrial ROS regulate NLRP3 inflammasome activation.

Abstruse

Reactive oxygen species (ROS) are integral components of multiple cellular pathways even though excessive or inappropriately localized ROS damage cells. ROS function as anti-microbial effector molecules and as signaling molecules that regulate such processes equally NF-kB transcriptional activity, the production of DNA-based neutrophil extracellular traps (NETs), and autophagy. The main sources of cellular ROS are mitochondria and NADPH oxidases (NOXs). In contrast to NOX-generated ROS, ROS produced in the mitochondria (mtROS) were initially considered to be unwanted past-products of oxidative metabolism. Increasing show indicates that mtROS accept been incorporated into signaling pathways including those regulating immune responses and autophagy. As metabolic hubs, mitochondria facilitate crosstalk between the metabolic state of the jail cell with these pathways. Mitochondria and ROS are thus a nexus of multiple pathways that determine the response of cells to disruptions in cellular homeostasis such as infection, sterile damage, and metabolic imbalance. In this review, we discuss the roles of mitochondria in the generation of ROS-derived anti-microbial effectors, the interplay of mitochondria and ROS with autophagy and the germination of DNA extracellular traps, and activation of the NLRP3 inflammasome by ROS and mitochondria.

Abbreviations

ASC

apoptosis-associated speck-like protein containing a caspase recruitment domain

CGD

chronic granulomatous disease

DAMP

damage-associated molecular pattern

Drp1

dynamin-related poly peptide ane

DUSP16/MKP-7

dual specificity protein phosphatase 16/mitogen-activated protein kinase phosphatase-7

ECSIT

evolutionarily conserved signaling intermediate in Price pathways

eis

enhanced intracellular survival gene

ERRα

estrogen-related receptor α

ETC

electron ship concatenation

G-CSF

granulocyte colony-stimulating gene

iNOS

inducible nitric oxide synthase

JNK

c-Jun N-terminal kinase

MAVS

mitochondrial antiviral signaling protein

Mtb

Mycobacterium tuberculosis

mtDAMP

mitochondrial damage-associated molecular pattern

mTOR

target of rapamycin, mammalian homolog

mtROS

ROS produced in the mitochondria

NETs

neutrophil extracellular traps

NLR

nucleotide binding domain-leucine rich repeat

NLRP3

nucleotide bounden domain-leucine rich echo, pyrin domain-containing iii

Nrf2

NF-E2-related factor 2

PAMP

pathogen-associated molecular design

PGC-1β

peroxisome proliferator-activated receptor γ coactivator-1β

PI3K-I

class I phosphoinositide iii-kinase

PMA

phorbol myristate acetate

RAGE

receptor for avant-garde glycation end-products

RIP1

receptor-interacting serine-threonine kinase 1

RIP3

receptor-interacting serine-threonine kinase three

ROS

reactive oxygen species, mainly superoxide and hydrogen peroxide

STAT1

signal transducer and activator of transcription 1

TORC1

target of rapamycin circuitous 1

TRAF6

tumor necrosis factor receptor-associated gene 6

TXNIP

thioredoxin-interacting protein

VSV

vesicular stomatitis virus

Keywords

Inflammasome

Mitochondria

Autophagy

Neutrophil extracellular traps

Immunity

Reactive oxygen species

Copyright © 2015 Published by Elsevier B.V.