Meeting Abstract
It has been proposed that mitochondria display a biphasic response to reactive oxygen species (ROS) accumulation referred to as mitohormesis. Under mitohormesis, low levels of ROS stimulate protection against oxidative damage, whereas high levels result in the accumulation of oxidative damage. The mechanisms that underlie improved function following low levels of ROS production are poorly understood. We evaluated the changes in mitochondrial performance in house mice following X-irradiation, which induces ROS production. Eight mice were maintained as unexposed controls and 8 mice were assigned to each of 5 groups that varied in time between x-ray exposure and mitochondrial isolation, including 1 hour, 1, 4, 7, and 10 days after x-ray. We measured mitochondrial respiratory function (RCR), ROS production (H2O2), and oxidative lipid damage (4-HNE) in the liver and the skeletal muscle from both hind legs and liver. In liver, RCR showed a right skewed U-shape curve in which day 1 and day 4 mice had significantly lower RCR than both non-irradiation control, and all other x-rayed mice. H2O2 and 4-HNE in liver displayed inverse U-shaped curves, with both peaking on day 4. Similar trends that were not significant were observe for RCR, H2O2 and 4-HNE levels in muscle. These data provide evidence that mitochondria become damaged in response to x-ray, but recover within one week of exposure. This represents the protective effect that ROS exposure has on mitochondrial function. Ongoing measurements of oxidative damage repair, mitophagy, mitochondrial apoptosis, and biogenesis will provide more comprehensive understanding of the mitohormetic response. The value of x-ray in inducing oxidative damage in experimental studies will be discussed.
