Abstract
Mitochondria are sensitive to oxidative stress, including that derived from ionizing radiation. To quantify the effects of exposure to environmental radionuclides on mitochondrial DNA (mtDNA) dynamics in wildlife, bank voles (Myodes glareolus) were collected from the chernobyl exclusion zone (CEZ), where animals are exposed to elevated levels of radionuclides, and from uncontaminated areas within the CEZ and elsewhere in Ukraine. Brains of bank voles from outside the CEZ were characterized by low mtDNA copy number and low mtDNA damage; by contrast, bank voles within the CEZ had high mtDNA copy number and high mtDNA damage, consistent with putative damaging effects of elevated radiation and a compensatory response to maintain sufficient functioning mitochondria. In animals outside the CEZ, the expression levels of PGC-1α gene and mtDNA copy number were positively correlated as expected from this gene’s prominent role in mitochondrial biogenesis; this PGC-1α-mtDNA copy number association is absent in samples from the CEZ. Our data imply that exposure to radionuclides is associated with altered mitochondrial dynamics, evident in level of mtDNA and mtDNA damage and the level of activity in mitochondrial synthesis.
Highlights
Mitochondria are the powerhouses of eukaryotic cells, involved in energy production, metabolism and cell signaling (Chinnery and Hudson 2013)
High mitochondrial DNA (mtDNA) copy number was significantly associated with greater damage to mtDNA (Table 1): bank voles from both chernobyl exclusion zone (CEZ) locations had significantly fewer undamaged mtDNA copies compared with animals from outside the CEZ (Table 1, Fig. 2b), albeit with a trend of more damage in the CEZ background areas (Table S3/ESM1)
We show that exposure to environmental radionuclides impacts mitochondrial homeostasis in the brains of bank voles via an increase in (1) mtDNA copy number and (2) mtDNA damage, and (3) can impact the association between PGC-1α expression and mtDNA copy number
Summary
Mitochondria are the powerhouses of eukaryotic cells, involved in energy production, metabolism and cell signaling (Chinnery and Hudson 2013). Each of which has multiple copies of its own circular genome (the mitochondrial DNA, mtDNA): mammalian somatic cells may contain up to 104 mtDNA copies The number of mitochondria and mtDNA genomes is dynamic and the organelles and their DNA can be replicated or degraded independently of the cell cycle (Michel et al 2012; Chinnery and Hudson 2013). Mitochondrial ROS are typically detoxified by antioxidants or can have important roles, such as cell signaling and immunological defense (Finkel and Holbrook 2000; Shokolenko et al 2009; Alexeyev et al 2013). Dysfunctional mitochondria and impaired clearance of damaged mitochondria have been associated with various diseases and accelerated molecular aging (Finkel and Holbrook 2000; Correia-Melo et al 2014)
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