Role of the Nrf2/ARE Pathway in the mtDNA Reparation

Mitochondrial DNA (mtDNA) is located in the mitochondrial matrix, in close proximity to major sources of reactive oxygen species (ROS) in the cell. This makes mtDNA one of the most susceptible components to damage in the cell. The nuclear factor E2-related factor 2/antioxidant response element (Nrf2...

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Bibliographic Details
Published in:Frontiers in bioscience (Landmark. Print) 2024-06, Vol.29 (6), p.218
Main Authors: Gureev, Artem P, Chernyshova, Ekaterina V, Krutskikh, Ekaterina P, Sadovnikova, Irina S, Tekutskaya, Elena E, Dorohova, Anna A
Format: Article
Language:English
Subjects:
Animals
Antioxidant Response Elements - genetics
base excision repair
brca1
BRCA1 Protein - genetics
BRCA1 Protein - metabolism
DNA Damage
DNA Repair
DNA, Mitochondrial - genetics
DNA, Mitochondrial - metabolism
Humans
mtdna
NF-E2-Related Factor 2 - genetics
NF-E2-Related Factor 2 - metabolism
nrf2/are pathway
p53
Signal Transduction
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
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Summary:Mitochondrial DNA (mtDNA) is located in the mitochondrial matrix, in close proximity to major sources of reactive oxygen species (ROS) in the cell. This makes mtDNA one of the most susceptible components to damage in the cell. The nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway is an important cytoprotective mechanism. It is well-studied and described that Nrf2 can regulate the expression of mitochondrial-targeted antioxidant systems in the cell, indirectly protecting mtDNA from damage. However, the Nrf2/ARE pathway can also directly impact on the mtDNA repair processes. In this review, we summarize the existing data on the impact of Nrf2 on mtDNA repair, primarily base excision repair (BER), as it is considered the main repair pathway for the mitochondrial genome. We explore the crosstalk between Nrf2/ARE, BRCA1, and p53 signaling pathways in their involvement in maintaining mtDNA integrity. The role of other repair mechanisms in correcting mismatched bases and double-strand breaks is discussed. Additionally, the review addresses the role of Nrf2 in the repair of noncanonical bases, which contribute to an increased number of mutations in mtDNA and can contaminate the nucleotide pool.
ISSN:2768-6698
2768-6701
2768-6698
DOI:10.31083/j.fbl2906218