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Review
. 2023 Oct 11;15(1):171.
doi: 10.1186/s13195-023-01322-6.

Mitochondrial SOS: how mtDNA may act as a stress signal in Alzheimer's disease

Isabelle K Gorham  1 , Robert C Barber  2 , Harlan P Jones  1 , Nicole R Phillips  3
Affiliations
Review

Mitochondrial SOS: how mtDNA may act as a stress signal in Alzheimer's disease

Isabelle K Gorham et al. Alzheimers Res Ther. .

Abstract

Background: Alterations in mitochondrial DNA (mtDNA) levels have been observed in Alzheimer's disease and are an area of research that shows promise as a useful biomarker. It is well known that not only are the mitochondria a key player in producing energy for the cell, but they also are known to interact in other important intracellular processes as well as extracellular signaling and communication. BODY: This mini review explores how cells use mtDNA as a stress signal, particularly in Alzheimer's disease. We investigate the measurement of these mtDNA alterations, the mechanisms of mtDNA release, and the immunological effects from the release of these stress signals.

Conclusion: Literature indicates a correlation between the release of mtDNA in Alzheimer's disease and increased immune responses, showing promise as a potential biomarker. However, several questions remain unanswered and there is great potential for future studies in this area.

Keywords: Alzheimer’s Disease; Inflammation; Mitochondria; Oxidative Stress; mtDNA.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Mechanisms of mtDNA release. Stressed, dysfunctional, and/or damaged mitochondria may release mtDNA in whole or in fragments as a stress response via MPT pores, mitochondrial exosome release, and/or mitochondrial membrane permeabilization in BAX/BAK apoptosis. These mechanisms may cause a decrease in intracellular mtDNA and an accumulation of extracellular mtDNA which can act as a DAMP and trigger immune responses. This figure was created with BioRender.com
See this image and copyright information in PMC

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