Work

Overexpression of Twinkle-helicase protects cardiomyocytes from genotoxic stress caused by reactive oxygen species

Year: 2013

Type: article

Abstract: Mitochondrial DNA (mtDNA) in adult human heart is characterized by complex molecular forms held together by junctional molecules of unknown biological significance. These junctions are not present in mouse hearts and emerge in humans during postnatal development, concomitant with increased demand for oxidative metabolism. To analyze the role of mtDNA organization during oxidative stress in cardiomyocytes, we used a mouse model, which recapitulates the complex mtDNA organization of human hearts by overexpression of the mitochondrial helicase, TWINKLE. Overexpression of TWINKLE rescued the oxidative damage induced replication stalling of mtDNA, reduced mtDNA point mutation load, and modified mtDNA rearrangements in heterozygous mitochondrial superoxide dismutase knockout hearts, as well as ameliorated cardiomyopathy in mice superoxide dismutase knockout in a p21-dependent manner. We conclude that mtDNA integrity influences cell survival and reason that tissue specific modes of mtDNA maintenance represent an adaptation to oxidative stress.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1303046110

Authors: Jaakko L. O. Pohjoismäki, Siôn L. Williams, Thomas Boettger, Steffi Goffart, Johnny Kim, Anu Suomalainen, Carlos T. Moraes, Thomas Braun

Institutions: University of Eastern Finland, Max Planck Institute for Heart and Lung Research, University of Miami, University of Helsinki, Helsinki University Hospital

Language: English

Topic: Mitochondrial Function and Pathology

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

OpenAlex ID: W1993968187

FWCI: 1.869

Cites: 46

Cited by: 44

Related to: 10