CHARACTERIZATION OF THE MOLECULAR FUNCTION AND REGULATION OF MOAP-1 IN NEURONS

Abstract

MOAP-1 IS A LOW ABUNDANCE PRO-APOPTOTIC PROTEIN THAT IS TIGHTLY REGULATED BY THE UBIQUITIN-PROTEASOME SYSTEM (UPS). APOPTOTIC STIMULI DRAMATICALLY UP-REGULATE MOAP-1 AND PROMOTE ITS INTERACTION WITH BAX AT THE OUTER MITOCHONDRIAL MEMBRANE (OMM) TO FACILITATE BAX-DEPENDENT APOPTOSIS. INDEED, MOAP-1 DEFICIENT ANIMALS DISPLAYED DRAMATIC RESISTANCE TO HEPATOCELLULAR APOPTOSIS TRIGGERED BY IN VIVO ACTIVATION OF FAS SIGNALING. IN CONTRAST TO OTHER TISSUES, MOAP-1 PROTEIN IS IN HIGH ABUNDANCE IN BRAIN. PRELIMINARY ANALYSIS SHOWED THAT MOAP-1 LOCALIZES WITH NEURONAL CELL BODIES IN BRAIN, RAISING THE INTERESTING POSSIBILITY THAT REGULATION AND POSSIBLY FUNCTION OF MOAP-1 IN NEURONS OF BRAIN COULD BE DISTINCT FROM OTHER ORGANS. IN THIS WORK, I INVESTIGATED THE FUNCTION OF MOAP-1 IN PRIMARY NEURONS AND MOUSE EMBRYONIC FIBROBLASTS (MEFS) DERIVED FROM MOAP-1 DEFICIENT MICE. MY DATA UNVEILED A PUTATIVE ROLE OF MOAP-1 IN REGULATING AUTOPHAGY AND MITOPHAGY. WE ALSO IDENTIFIED A NOVEL BRAIN-SPECIFI