Mechanisms of Energy Metabolism in Skeletal Muscle Mitochondria Following Radiation Exposure.

Kim Kim,Yi Yi,Lee Lee

doi:10.3390/cells8090950

Abstract

An understanding of cellular processes that determine the response to ionizing radiation exposure is essential for improving radiotherapy and assessing risks to human health after accidental radiation exposure. Radiation exposure leads to many biological effects, but the mechanisms underlying the metabolic effects of radiation are not well known. Here, we investigated the effects of radiation exposure on the metabolic rate and mitochondrial bioenergetics in skeletal muscle. We show that ionizing radiation increased mitochondrial protein and mass and enhanced proton leak and mitochondrial maximal respiratory capacity, causing an increase in the fraction of mitochondrial respiration devoted to uncoupling reactions. Thus, mice and cells treated with radiation became energetically efficient and displayed increased fatty acid and amino acid oxidation metabolism through the citric acid cycle. Finally, we demonstrate that radiation-induced alterations in mitochondrial energy metabolism involved adenosine monophosphate-activated kinase signaling in skeletal muscle. Together, these results demonstrate that alterations in mitochondrial mass and function are important adaptive responses of skeletal muscle to radiation.

Highlights

Ionizing radiation (IR) is used as a treatment for many cancers and is an important diagnostic tool, but it is a genetic toxicant that can negatively affect various cellular processes [1].improvements in the ability to detect and treat cancer have resulted in a 60% survival rate of five years after cancer diagnosis, and about two-thirds of these survivors are receiving radiation therapy
To confirm the expected effects of IR on levels of tricarboxylic acid (TCA) cycle intermediates in skeletal muscle tissues and body fluids of Imprinting control region (ICR) mice, we performed a metabolic analysis of intracellular TCA cycle intermediates and glutamate/glutamine—two essential amino acids [23] that can be derived from TCA
Twenty-four hours after 2 Gy of IR exposure, lactate levels increased in serum, but were not altered in skeletal muscle (Figure 1A), whereas acetyl-coenzyme A (CoA) and malate levels decreased in skeletal muscle, but not in serum (Figure 1C,D)

Summary

Introduction

Ionizing radiation (IR) is used as a treatment for many cancers and is an important diagnostic tool, but it is a genetic toxicant that can negatively affect various cellular processes [1].improvements in the ability to detect and treat cancer have resulted in a 60% survival rate of five years after cancer diagnosis, and about two-thirds of these survivors are receiving radiation therapy. Ionizing radiation (IR) is used as a treatment for many cancers and is an important diagnostic tool, but it is a genetic toxicant that can negatively affect various cellular processes [1]. The late effect of radiation is an area of clinical interest [2]. IR induces factors that are important in modulating mitochondrial biogenesis, which is related to cell survival: mitochondria have been reported to be the primary target for radiation-induced apoptosis [3]. This organelle may play a role in radiation-induced intra- and intercellular signaling [4,5]. The effects of IR on mitochondria have been much less intensively investigated than those on the cell nucleus

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Discussion

Conclusion