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Neurosci Lett. 2019 Sep 25;710:132931. doi: 10.1016/j.neulet.2017.06.050. Epub 2017 Jun 28.

Inflammation and mitochondrial dysfunction: A vicious circle in neurodegenerative disorders?

Author information

1
Dept. of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: j.vanhorssen@vumc.nl.
2
Dept. of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.

Abstract

Experimental evidence supports an intricate association between inflammation and mitochondrial dysfunction as main contributors of neurological diseases. Inflammatory mediators produced by activated microglia and infiltrated immune cells trigger intracellular signalling cascades that can alter cellular mitochondrial metabolism. Cytokines, particularly tumor necrosis factor-alpha, impede mitochondrial oxidative phosphorylation and associated ATP production and instigate mitochondrial reactive oxygen species production. This culminates in mitochondrial membrane permeabilization, altered mitochondrial dynamics and might ultimately result in cell death. When severely injured mitochondria are not appropriately removed by mitophagy they can release their contents into the cytosol and extracellular environment and thereby amplify the inflammatory process. Here we provide a comprehensive overview on how inflammatory mediators impair mitochondrial metabolism and discuss how defective mitochondria can elicit and potentiate an inflammatory response.

KEYWORDS:

Cytokines; Microglia; Mitochondria; Neurodegeneration; Neuroinflammation

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