Characterization of the Drosophila HtrA2/OMI Ortholog, a Mitochondrial Protein of Pro-apoptotic Function

While mitochondria are traditionally associated with energy production, recent studies identified its function in controlling the onset of apoptosis. Mitochondrial apoptotic control results from sequestering pro-apoptotic proteins, which are secreted following cellular stress. HtrA2/OMI is secreted from mitochondria to the cytosol following apoptotic induction, binds and degrades the inhibitor of apoptosis protein, XIAP in mammals, activating the caspase cascade. This study characterizes the expression of Drosophila HtrA2/OMI, a mitochondrial protein, its processing by Rhomboid-7 and demonstrates its pro-apoptotic function. Following exposure to apoptotic stress, dOMI is secreted from mitochondria and its expression profile displays an increase in a cleaved form consistent with Rhomboid-7 processing. dOMI expression resulted in sensitization of cells to apoptotic stress, observed through an increase in caspase activity. These data further validate the use of Drosophila in the study of mitochondrial driven apoptosis while implicating a potential role for Rhomboid-7 in apoptosis through proteolytic cleavage of dOMI.MAS