Cellular and Molecular Life Sciences

, Volume 69, Issue 18, pp 2999–3013

Mitochondrial dysfunction and oxidative stress activate inflammasomes: impact on the aging process and age-related diseases

  • Antero Salminen
  • Johanna Ojala
  • Kai Kaarniranta
  • Anu Kauppinen
Review

DOI: 10.1007/s00018-012-0962-0

Cite this article as:
Salminen, A., Ojala, J., Kaarniranta, K. et al. Cell. Mol. Life Sci. (2012) 69: 2999. doi:10.1007/s00018-012-0962-0

Abstract

Oxidative stress and low-grade inflammation are the hallmarks of the aging process and are even more enhanced in many age-related degenerative diseases. Mitochondrial dysfunction and oxidative stress can provoke and potentiate inflammatory responses, but the mechanism has remained elusive. Recent studies indicate that oxidative stress can induce the assembly of multiprotein inflammatory complexes called the inflammasomes. Nod-like receptor protein 3 (NLRP3) is the major immune sensor for cellular stress signals, e.g., reactive oxygen species, ceramides, and cathepsin B. NLRP3 activation triggers the caspase-1-mediated maturation of the precursors of IL-1β and IL-18 cytokines. During aging, the autophagic clearance of mitochondria declines and dysfunctional mitochondria provoke chronic oxidative stress, which disturbs the cellular redox balance. Moreover, increased NF-κB signaling observed during aging could potentiate the expression of NLRP3 and cytokine proforms enhancing the priming of NLRP3 inflammasomes. Recent studies have demonstrated that NLRP3 activation is associated with several age-related diseases, e.g., the metabolic syndrome. We will review here the emerging field of inflammasomes in the appearance of the proinflammatory phenotype during the aging process and in age-related diseases.

Keywords

AgeingAutophagyInflammasomeInflammationNF-κBNLRP3

Abbreviations

AIM2

Absent in melanoma 2

ASC

Apoptosis-associated speck-like protein containing CARD domain

CARD

Caspase recruitment domain

CSF

Cerebrospinal fluid

DAMP

Damage-associated molecular pattern

dsDNA

Double-stranded DNA

ER

Endoplasmic reticulum

FPR

Formyl peptide receptor

HMGB1

High-mobility group protein B1

IAPP

Islet amyloid polypeptide

IFNβ

Interferon β

IKK

Inhibitory-κB kinase

IL

Interleukin

LPS

Lipopolysaccharide

LRR

Leucine-rich repeat

MAM

Mitochondria-associated ER membrane

MAVS

Mitochondrial antiviral signaling protein

MnSOD

Mitochondrial manganese superoxide dismutase

mtDNA

Mitochondrial DNA

NADPH

Nicotinamide adenine dinucleotide phosphate

NF-κB

Nuclear factor-κB

NAIP5

NLR family, apoptosis inhibitory protein

NLR

Nucleotide-binding domain leucine-rich repeat-containing receptor family

NLRC4

NLR family, CARD-containing 4

NLRP3

NLR family, pyrin domain-containing 3

NOD1

Nucleotide-binding oligomerization domain-containing protein 1

NOS

Nitric-oxide synthase

Nox1-4

NADPH oxidases 1–4

NRF2

Nuclear factor E2-related factor 2

P2X7

P2X purinoceptor 7

PMN

Polymorphonuclear neutrophil

PYD

Pyrin domain

RIG-1

Retinoic acid inducible gene-1

ROS

Reactive oxygen species

SAMP

Senescence-accelerated prone mouse

STAT1

Signal transducer and activator of transcription 1

TLR

Toll-like receptors

TNF

Tumour necrosis factor

TRAF

TNF receptor-associated factor

TRIM30

Tripartite-motif protein 30

TRX

Thioredoxin

TXNIP

Thioredoxin-interacting protein

UCP

Uncoupling protein

UPRmt

Mitochondrial unfolded protein response

UVB

Ultraviolet B

Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  • Antero Salminen
    • 1
    • 2
  • Johanna Ojala
    • 1
  • Kai Kaarniranta
    • 3
    • 4
  • Anu Kauppinen
    • 3
  1. 1.Department of Neurology, Institute of Clinical MedicineUniversity of Eastern FinlandKuopioFinland
  2. 2.Department of NeurologyUniversity Hospital of KuopioKuopioFinland
  3. 3.Department of Ophthalmology, Institute of Clinical MedicineUniversity of Eastern FinlandKuopioFinland
  4. 4.Department of OphthalmologyUniversity Hospital of KuopioKuopioFinland