HIGH AMBIENT TEMPERATURES ARE A MAJOR PROBLEM FOR THE DAIRY INDUSTRY. DAIRY CATTLE HAVE BEEN BRED TO BE COPIOUS MILK PRODUCERS, BUT THIS HAS ALSO REDUCED THEIR ABILITY TO TOLERATE ELEVATED TEMPERATURES. HEAT STRESSED COWS ARE MORE SUSCEPTIBLE TO DISEASE, HAVE LOWER FERTILITY, AND PRODUCE LESS MILK. THIS COMES WITH A PRICE TAG OF OVER $1 BILLION ANNUALLY FOR THE U.S. DAIRY INDUSTRY. AS DEMAND FOR DAIRY PRODUCTS INCREASES WORLDWIDE AND AS EARTH'S TEMPERATURE CONTINUES TO RISE, WE NEED TO HAVE A BETTER UNDERSTANDING OF WHY HEAT STRESSED COWS PRODUCE LESS MILK IN ORDER TO DEVELOP NOVEL STRATEGIES TO COMBAT HEAT EFFECTS ON DAIRY CATTLE. RECENT RESEARCH POINTS TO A SPECIFIC CELLULAR ORGANELLE, THE MITOCHONDRION, THAT MAY PLAY A PART IN THE REDUCED MILK YIELD OF HEAT STRESSED COWS. MITOCHONDRIA ARE SMALL STRUCTURES IN CELLS THAT HOUSE THE MACHINERY TO MAKE ENERGY AND THEY ALSO PRODUCE SOME OF THE NUTRIENT PRECURSORS NEEDED TO MAKE MILK. WHEN MITOCHONDRIA ARE DAMAGED, THEIR ABILITY TO PRODUCE ENERGY IS COMPROMISED AND THIS CAN RESULT IN THE FORMATION OF MOLECULES THAT CAUSE OXIDATIVE STRESS AND DAMAGE TO AN ORGAN. HIGH TEMPERATURES APPEAR TO DAMAGE MITOCHONDRIA AND CAN CAUSE CHANGES IN BLOOD HORMONES THAT REGULATE MITOCHONDRIAL FUNCTION. HOWEVER, IT IS UNCLEAR IF AND HOW HEAT STRESS AFFECTS MITOCHONDRIAL FUNCTION AND ULTIMATELY MILK PRODUCTION. OUR HYPOTHESIS IS THAT HEAT STRESS IMPAIRS ENERGY PRODUCTION IN MITOCHONDRIA AND CAUSES OXIDATIVE DAMAGE IN TISSUES CRITICAL FOR LACTATION. OUR STUDY WILL ADDRESS THE FOLLOWING SPECIFIC AIMS:AIM 1. TO ASSESS MITOCHONDRIAL FUNCTION IN THE LIVER AND MAMMARY GLAND, TWO KEY ORGANS THAT ENABLE MILK PRODUCTION, IN HEAT STRESSED LACTATING DAIRY COWS. AIM 2. TO IDENTIFY HORMONAL PATHWAYS THAT MAY STIMULATE MITOCHONDRIAL DYSFUNCTION UNDER HEAT STRESS CONDITIONS. WE ANTICIPATE THAT HEAT STRESSED COWS WILL HAVE DYSFUNCTIONAL MITOCHONDRIA THAT PRODUCE LESS ENERGY AND CAUSE OXIDATIVE STRESS, WHICH WILL COMPROMISE MILK PRODUCTION. WE EXPECT THAT EPINEPHRINE, A HORMONE THAT REGULATES MITOCHONDRIA AND IS ELEVATED IN HEAT STRESSED COWS, CONTRIBUTES TO MITOCHONDRIAL DYSFUNCTION WITH HEAT STRESS. OUR STUDY WILL ADDRESS A CRITICAL KNOWLEDGE GAP REGARDING THE BIOLOGICAL MECHANISMS THAT CONTRIBUTE TO LOW MILK PRODUCTION IN HEAT STRESSED COWS. FURTHER, RESULTS OF THIS STUDY COULD BE USED TO DEVELOP INTERVENTIONS, SUCH AS MITOCHONDRIAL-TARGETED THERAPIES, AND BREEDING PROGRAMS THAT INCORPORATE MITOCHONDRIAL TRAITS TO IMPROVE MILK PRODUCTION IN A WARMING WORLD.