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Do Mitochondrial DNA Mutations Play a Key Role in the Chronification of Sterile Inflammation? Special Focus on Atherosclerosis

[ Vol. 27 , Issue. 2 ]

Author(s):

Alexander N. Orekhov*, Elena V. Gerasimova, Vasily N. Sukhorukov, Anastasia V. Poznyak* and Nikita G. Nikiforov   Pages 274 - 290 ( 17 )

Abstract:


Background: The aim of the elucidation of mechanisms implicated in the chronification of inflammation is to shed light on the pathogenesis of disorders that are responsible for the majority of the incidences of diseases and deaths, and also causes of ageing. Atherosclerosis is an example of the most significant inflammatory pathology. The inflammatory response of innate immunity is implicated in the development of atherosclerosis arising locally or focally.

Modified low-density lipoprotein (LDL) was regarded as the trigger for this response. No atherosclerotic changes in the arterial wall occur due to the quick decrease in inflammation rate. Nonetheless, the atherosclerotic lesion formation can be a result of the chronification of local inflammation, which, in turn, is caused by alteration of the response of innate immunity.

Objective: In this review, we discussed potential mechanisms of the altered response of the immunity in atherosclerosis with a particular emphasis on mitochondrial dysfunctions.

Conclusion: A few mitochondrial dysfunctions can be caused by the mitochondrial DNA (mtDNA) mutations. Moreover, mtDNA mutations were found to affect the development of defective mitophagy. Modern investigations have demonstrated the controlling mitophagy function in response to the immune system. Therefore, we hypothesized that impaired mitophagy, as a consequence of mutations in mtDNA, can raise a disturbed innate immunity response, resulting in the chronification of inflammation in atherosclerosis.

Keywords:

Atherosclerosis, chronification of inflammation, defective mitophagy, innate immunity, mitochondrial dysfunction, modified LDL.

Affiliation:

Institute of General Pathology and Pathophysiology, 125315 Moscow, V. A. Nasonova Institute of Rheumatology, 115522 Moscow, Institute of Human Morphology, 117418 Moscow, Institute for Atherosclerosis Research, 121609 Moscow, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow



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