MITOCHONDRIA ARE THE POWERHOUSES OF THE CELL, WHICH MAKE UP 30% OF THE VOLUME OF CARDIAC MYOCYTES. THEY PROVIDE THE CRUCIAL ENERGY SUPPLY NEEDED FOR THE HEART TO BEAT AND TO PROVIDE BLOOD AND OXYGEN THROUGHOUT THE BODY. THE GOAL OF THIS GROUND-BASED TISSUE SHARING PROJECT IS TO DETERMINE THE EFFECTS OF LOW DOSE/LOW FLUENCE SPACE IONIZING RADIATION ON THE MITOCHONDRIAL STRESS RESPONSE IN THE HEART. WE WILL EXAMINE HEART TISSUE COLLECTED BY OUR COLLABORATOR DR. EDOUARD AZZAM, WHOSE CURRENT NASA-FUNDED PROJECT IS INVESTIGATING "OXIDATIVE STRESS AND THE CANCER RISK OF SPACE RADIATION". HIS STUDY EMPLOYS 10 MONTH-OLD MALE MICE, WHICH IS AN AGE THAT IS EQUIVALENT TO ACTIVE ASTRONAUTS WHO ARE BETWEEN 35-55 YEARS OLD. THESE MICE ARE EXPOSED TO LOW MEAN ABSORBED DOSES OF ISOVELOCITY (1 GEV/N) PROTONS OR HIGH ATOMIC NUMBER, HIGH ENERGY (HZE) PARTICLES, WHICH ARE A COMPONENT OF GALACTIC COSMIC RAYS. ANOTHER GROUP OF MICE ARE EXPOSED TO 137CS "{RAYS AS REFERENCE RADIATION. USING THESE HEART SAMPLES, WE WILL EMPLOY HISTOLOGICAL TECHNIQUES, AS WELL AS BIOCHEMICAL AND MOLECULAR BIOLOGICAL APPROACHES TO MEASURE BIOMARKERS OF THE MITOCHONDRIAL STRESS RESPONSE IN HEART IN RESPONSE TO HZE PARTICLES AND REFERENCE RADIATION. CARDIAC INFLAMMATION AND FIBROSIS WILL BE EXAMINED HISTOLOGICALLY. RADIATION-INDUCED CHANGES IN MITOCHONDRIAL DNA COPY NUMBER AND DAMAGE AND MITOCHONDRIAL RNA AND PROTEIN EXPRESSION WILL BE MEASURED. SPACE RADIATION HAS BEEN SHOWN TO INDUCE REACTIVE OXYGEN SPECIES, WHICH OXIDATIVELY DAMAGE NUCLEIC ACIDS, PROTEINS AND LIPIDS. WE WILL ALSO DETERMINE THE RELATIVE PROTEIN LEVELS AND ACTIVITY OF CRUCIAL MITOCHONDRIAL STRESS RESPONSE PROTEINS, WHICH ARE EXPECTED TO MITIGATE CARDIAC INJURY THAT MAY BE CAUSED BY RADIATION-INDUCED OXIDATIVE DAMAGE. THE RESULTS OF THESE EXPERIMENTS WILL FILL KNOWLEDGE GAPS ABOUT RADIATION-INDUCED DEGENERATION OR INJURY TO CARDIAC MITOCHONDRIA, AND THE ADAPTIVE STRESS RESPONSE MECHANISMS, WHICH POTENTIALLY PROMOTE OR MITIGATE POTENTIAL RISKS TO THE HEART.