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Mitochondrial maintenance under oxidative stress depends on mitochondrially localised α-OGG1.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Lia, Debora 
Reyes, Aurelio 
de Melo Campos, Julliane Tamara Araújo 
Piolot, Tristan 
Baijer, Jan 

Abstract

Accumulation of 8-oxoguanine (8-oxoG) in mitochondrial DNA and mitochondrial dysfunction have been observed in cells deficient for the DNA glycosylase OGG1 when exposed to oxidative stress. In human cells, up to eight mRNAs for OGG1 can be generated by alternative splicing and it is still unclear which of them codes for the protein that ensures the repair of 8-oxoG in mitochondria. Here, we show that the α-OGG1 isoform, considered up to now to be exclusively nuclear, has a functional mitochondrial-targeting sequence and is imported into mitochondria. We analyse the sub-mitochondrial localisation of α-OGG1 with unprecedented resolution and show that this DNA glycosylase is associated with DNA in mitochondrial nucleoids. We show that the presence of α-OGG1 inside mitochondria and its enzymatic activity are required to preserve the mitochondrial network in cells exposed to oxidative stress. Altogether, these results unveil a new role of α-OGG1 in the mitochondria and indicate that the same isoform ensures the repair of 8-oxoG in both nuclear and mitochondrial genomes. The activity of α-OGG1 in mitochondria is sufficient for the recovery of organelle function after oxidative stress.

Description

Keywords

8-oxoG, DNA repair, Mitochondria, OGG1, Cell Cycle, Cell Line, Tumor, DNA Glycosylases, DNA, Mitochondrial, Guanine, HEK293 Cells, Humans, Mitochondria, Mitochondrial Membranes, Oxidative Stress, RNA, Small Interfering, Reactive Oxygen Species, Transfection

Journal Title

J Cell Sci

Conference Name

Journal ISSN

0021-9533
1477-9137

Volume Title

131

Publisher

The Company of Biologists
Sponsorship
Medical Research Council (MC_UP_1002/1)
Medical Research Council (MC_UU_00015/8)
Medical Research Council (MC_UU_00015/7)