Mechanisms of Energy Metabolism in Skeletal Muscle Mitochondria Following Radiation Exposure

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.

Leucine Supplementation: A Novel Strategy for Modulating Lipid Metabolism and Energy Homeostasis

“…The skeletal muscle plays a crucial role in energy homeostasis by clearing serum-free fatty acid, whole-body FAO, and lipid utilization [72]. There is a growing body of evidence suggesting that defective metabolism in muscle mitochondria and subsequent impaired ability to oxidize fatty acids may be a causative factor in the accumulation of intramuscular fat [59,73,74]. In particular, increased mitochondrial content and function is closely associated with enhanced oxidative capacity of muscle fibers, leading to an improved muscle health and overall health and well-being [75].…”

Metabolic profiles of whole serum and serum-derived exosomes are different in head and neck cancer patients treated by radiotherapy

“…Our study revealed that RT affected serum levels of several amino acids, biogenic amines, sugars, nucleotides, lipids, and fatty acids, which mirrored potential RT-induced changes in a plethora of metabolic pathways ongoing in a patient's body. It was previously reported that altered metabolism of amino acid plays an important role in the response of HNC patients to RT [36]. For example, Boguszewicz and co-workers [4] demonstrated that decreased serum level of alanine, the main substrate for gluconeogenesis during fasting and cachexia, correlated with the acute radiation toxicity-associated weight loss in HNC patients undergoing RT.…”

Metabolic Profiles of Whole Serum and Serum-Derived Exosomes Are Different in Head and Neck Cancer Patients Treated by Radiotherapy

“…It is noteworthy that different radiation-related mechanisms might contribute to metabolic changes observed in samples collected one month after the end of RT, including toxicity induced by radiation in normal tissues and a reduced number of cancer cells. It was previously reported that the altered metabolism of amino acid plays an important role in the response of HNC patients to RT [ 36 ]. For example, Boguszewicz and co-workers [ 4 ] demonstrated that a decreased serum level of alanine, the main substrate for gluconeogenesis during fasting and cachexia, correlated with the acute radiation toxicity-associated weight loss in HNC patients undergoing RT.…”