Project Grant 2339182

CAREER: MITOCHONDRIAL GENOME PARTITIONING AND QUALITY CONTROL -THIS PROJECT IS FOCUSED ON MITOCHONDRIA, OFTEN CALLED ?THE POWERHOUSE OF THE CELL?. MITOCHONDRIA ARE SPECIALIZED CELLULAR COMPARTMENTS THAT ARE ESSENTIAL FOR ENERGY TRANSDUCTION, AND WHICH CONTAIN THEIR OWN SPECIAL GENES THAT ARE MAINTAINED INDEPENDENTLY OF THE REST OF THE DNA IN THE CELL. WHILE MUCH IS KNOWN ABOUT THE INHERITANCE OF GENES THAT RESIDE IN THE CELL NUCLEUS, COMPARATIVELY LITTLE IS UNDERSTOOD ABOUT HOW MITOCHONDRIAL GENES ARE INHERITED. THE GOALS OF THIS PROJECT ARE TO REVEAL, AT THE MOLECULAR AND ORGANELLE LEVELS, THE MECHANISMS OF MITOCHONDRIAL GENOME INHERITANCE AND HOW IT RELATES TO MITOCHONDRIAL FUNCTION. ONCE THIS IS KNOWN, IT MAY BE POSSIBLE TO TUNE ENERGY PRODUCTION UP OR DOWN IN CELLS BY MANIPULATING THE NUMBER AND QUALITY OF MITOCHONDRIAL GENOMES. THE BROADER IMPACTS OF THE WORK INVOLVE THE INTRINSIC MERIT OF THE RESEARCH AS VIRTUALLY ALL EUKARYOTIC CELLS CONTAIN MITOCHONDRIA. IN ADDITION, TRAINING OPPORTUNITIES WILL BE PROVIDED FOR STUDENTS FROM UC BERKELEY, ALONG WITH THOSE FROM A LOCAL COMMUNITY COLLEGE. MITOCHONDRIAL OXIDATIVE FUNCTION IS AT THE NEXUS OF CELLULAR METABOLISM IN ANIMAL CELLS. FOR EXAMPLE, OVER 90% OF THE OXYGEN IN EVERY HUMAN BREATH IS CONSUMED IN MITOCHONDRIA BY THE ELECTRON TRANSPORT CHAIN, GENERATING A TRANS-MEMBRANE PROTON GRADIENT THAT NOT ONLY MAKES ATP BUT IS NECESSARY FOR MULTIPLE ANABOLIC FUNCTIONS OF MITOCHONDRIA INCLUDING THE SYNTHESIS OF AMINO ACIDS, NUCLEOTIDES, AND LIPIDS. MITOCHONDRIAL FORM AND FUNCTION ARE INTEGRATED BY MOLECULAR MACHINES THAT DIVIDE AND FUSE ORGANELLE FRAGMENTS TO AFFECT INHERITANCE OF THE POLYPLOID MITOCHONDRIAL GENOME, GIVING RISE TO A DYNAMIC NETWORK THAT SPANS THE CYTOPLASM AND IS RESPONSIVE TO METABOLIC SIGNALS AND ENERGY DEMANDS ON THE MICRON SCALE. UNDERSTANDING HOW MITOCHONDRIA ARE REMODELED TO ENSURE THAT MITOCHONDRIAL GENOMES ARE PRESENT IN SUFFICIENT ABUNDANCE AND POSITIONING TO MEET ENERGY DEMANDS IS A MAJOR OPEN QUESTION IN BIOLOGY. THE RESULTS OF THIS PROJECT WILL REVEAL HOW MITOCHONDRIAL DNA TRANSMISSION IS MECHANISTICALLY LINKED TO MITOCHONDRIAL DYNAMICS, IDENTIFY MOLECULAR TETHER(S) THAT POSITION MITOCHONDRIAL GENOMES IN ORGANELLE NETWORKS, AND GENERALLY EXPAND OUR UNDERSTANDING OF MITOCHONDRIAL QUALITY CONTROL. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE PLANNED FOR THIS AWARD.