SIRT3 gene expression: a link between inherited mitochondrial DNA variants and oxidative stress.
Signaling pathways between mitochondrial and nuclear genomes are activated to preserve cellular homeostasis, especially in the event of stress. Using cybrid cell lines, we investigated whether inherited mitochondrial DNA (mtDNA) variants modulate the expression profiles of mammalian sirtuins (SIRT1-7) under oxidative stress conditions. We found that the expression of the SIRT3 gene was down-regulated in cybrids harboring mtDNA of the J haplogroup, which correlated with mitochondrial function, resulting in a decline of NAD(+)/NADH and ATP levels. Overall, the data reported here highlight a link between SIRT3, mitochondrial DNA variability and mitochondrial functionality, three fundamental components of the cellular stress response.
Department of Cell Biology, University of Calabria, Rende, Italy.
Patrizia
P
D'Aquila
Giuseppina
G
Rose
Maria Luisa
ML
Panno
Giuseppe
G
Passarino
Dina
D
Bellizzi
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D053938:DNA Fragmentation; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods; D014644:Genetic Variation; D006801:Humans; D008322:Mammals; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D056566:Sirtuin 3 / Q000235:genetics* / Q000378:metabolism
D000975:Antioxidants; D004272:DNA, Mitochondrial; D012333:RNA, Messenger; D009243:NAD; D000255:Adenosine Triphosphate; C466093:SIRT3 protein, human; D056566:Sirtuin 3