Mitochondrial DNA: Cellular Genotoxic Stress Sentinel

Overview

Journal Trends Biochem Sci

Specialty Biochemistry

Date 2021 Jun 5

PMID 34088564

Citations 46

Authors

Zheng Wu

Alva G Sainz

Gerald S Shadel

Affiliations

Soon will be listed here.

Abstract

High copy number, damage prone, and lean on repair mechanisms are unique features of mitochondrial DNA (mtDNA) that are hard to reconcile with its essentiality for oxidative phosphorylation, the primary function ascribed to this maternally inherited component of our genome. We propose that mtDNA is also a genotoxic stress sentinel, as well as a direct second messenger of this type of cellular stress. Here, we discuss existing evidence for this sentinel/effector role through the ability of mtDNA to escape the confines of the mitochondrial matrix and activate nuclear DNA damage/repair responses via interferon-stimulated gene products and other downstream effectors. However, this arrangement may come at a cost, leading to cancer chemoresistance and contributing to inflammation, disease pathology, and aging.

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