Mechanisms of Energy Metabolism in Skeletal Muscle Mitochondria Following Radiation Exposure

• Published in: Cells (Basel, Switzerland) Vol. 8; no. 9; p. 950
• Main Authors: Kim, Eun Ju, Lee, Minyoung, Kim, Da Yeon, Kim, Kwang Il, Yi, Jae Youn
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.08.2019; MDPI
• Subjects: Adenosine; Adenosine kinase; Amino acids; AMP; AMPK; Animals; Apoptosis; Bioenergetics; Biosynthesis; Cell culture; Cells, Cultured; Citric acid; CPT1; Energy; Energy Metabolism; Enzymes; Fatty acids; Gene expression; Homeostasis; Ionizing radiation; Kinases; Male; Metabolic rate; Metabolism; Mice; Mice, Inbred ICR; Mitochondria; Mitochondria - metabolism; Mitochondria - radiation effects; mitochondrial bioenergetics; Mitochondrial DNA; Muscle, Skeletal - metabolism; Muscle, Skeletal - radiation effects; Musculoskeletal system; Oxidation; PGC1; Phosphorylation; Radiation Exposure; Radiation therapy; Skeletal muscle; Tricarboxylic acid cycle; Whole-Body Irradiation; X-Rays; Canada; United States > US; Germany; PGC1; AMPK; CPT1; ionizing radiation; mitochondrial bioenergetics
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells8090950

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.