Mitochondrial reactive oxygen species-mediated genomic instability in low-dose irradiated human cells through nuclear retention of cyclin D1.

Abstract

Mitochondria are associated with various radiation responses, including adaptive responses, mitophagy, the bystander effect, genomic instability, and apoptosis. We recently identified a unique radiation response in the mitochondria of human cells exposed to low-dose long-term fractionated radiation (FR). Such repeated radiation exposure inflicts chronic oxidative stresses on irradiated cells via the continuous release of mitochondrial reactive oxygen species (ROS) and decrease in cellular levels of the antioxidant glutathione. ROS-induced oxidative mitochondrial DNA (mtDNA) damage generates mutations upon DNA replication. Therefore, mtDNA mutation and dysfunction can be used as markers to assess the effects of low-dose radiation. In this study, we present an overview of the link between mitochondrial ROS and cell cycle perturbation associated with the genomic instability of low-dose irradiated cells. Excess mitochondrial ROS perturb AKT/cyclin D1 cell cycle signaling via oxidative inactivation of protein phosphatase 2A after low-dose long-term FR. The resulting abnormal nuclear accumulation of cyclin D1 induces genomic instability in low-dose irradiated cells.

• Authors: Tsutomu Shimura, Naoki Kunugita
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 15 Issue 11 Pg. 1410-4 (Jun 02 2016) ISSN: 1551-4005 [Electronic] United States
• PMID: 27078622 (Publication Type: Journal Article, Review)

Chemical References

• Antioxidants
• CCND1 protein, human
• DNA, Mitochondrial
• Reactive Oxygen Species
• Cyclin D1
• Proto-Oncogene Proteins c-akt
• Glutathione

Topics

• Antioxidants (metabolism)
• Apoptosis (genetics, radiation effects)
• Cell Cycle (genetics, radiation effects)
• Cell Nucleus (metabolism, radiation effects)
• Cells, Cultured
• Cyclin D1 (genetics, metabolism)
• DNA Damage
• DNA Replication (radiation effects)
• DNA, Mitochondrial (genetics, metabolism)
• Gamma Rays
• Gene Expression Regulation
• Genomic Instability
• Glutathione (antagonists & inhibitors, metabolism)
• Humans
• Mitochondria (metabolism, radiation effects)
• Mitophagy (genetics, radiation effects)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Reactive Oxygen Species (agonists, metabolism)
• Signal Transduction