Back
Acta Physiologica 2011; Volume 202, Supplement 685
Scandinavian Physiological Society's Annual Meeting
8/12/2011-8/14/2011
Bergen, Norway
IMPACT OF MITOCHONDRIAL DNA ON STEM CELL DIFFERENTIATION -RESULTS FROM A NEURONAL MODEL
Abstract number: 5.1.4
WANG1,3 W, ESBENSEN4 Y, KUNKE2,3 D, SUGANTHAN2,4 R, RACHEK5 L, BJORAS2,3 M, EIDE1,3 L
1Department of Medical Biochemistry and
2Department of Microbiology, Institute of Clinical Medicine, Oslo University Hospital, Norway,
3Centre of Molecular Biology and Neuroscience, University of Oslo, Norway,
4Institute of Clinical Epidemiology and Molecular Biology, Faculty Division Akershus University Hospital, University of Oslo, Lrenskog, Norway,
5Department of Cell Biology & Neuroscience, University of South Alabama, Alabama. Email: [email protected]
Aim:
Subtle manipulations of the cellular redox state affect mitochondrial DNA (mtDNA) in addition to regulating the Neural Stem Cell (NSC) differentiation lineage, alluding to a molecular link between mtDNA integrity and differentiation regulation.
Methods:
mtDNA damage in NSC was manipulated either by exogenous agents or by regulating mtDNA repair capacity, and the resulting effects on NSC differentiation were evaluated.
Results:
The DNA repair protein 8-oxoguanine DNA glycosylase (OGG1) is essential for repair of mtDNA damage in NSCs. Mitochondrial activation during differentiation induce mtDNA damage in ogg1-/-NSCs and shifts NSC differentiation direction towards astrocytic lineage, similar as wt NSCs subjected to mtDNA damaging insults. Antioxidant treatments to reverse mtDNA damage accumulation increased neurogenesis in ogg1-/-cells. Overexpressing OGG1 in mitochondria in ogg1-/-NSCs reduced mtDNA damage accumulation and resulted in elevated neurogenesis.
Conclusion:
Our results unravel a novel interdependence between mtDNA integrity and NSC differentiation fate, suggesting that that mtDNA damage is the primary signal for elevated astrogenesis and lack of neurogenesis during repair of neuronal injury.
To cite this abstract, please use the following information:
Acta Physiologica 2011; Volume 202, Supplement 685 :5.1.4