Disrupted in schizophrenia 1 (DISC1): subcellular targeting and induction of ring mitochondria

Several independent studies have identified Disrupted In Schizophrenia 1 (DISC1) as a potential susceptibility factor in the pathogenesis of schizophrenia and severe recurrent major depression. To identify potential mechanisms by which DISC1 may influence development of psychiatric illness, we investigated the cellular consequences of recombinant DISC1 expression in COS-7 cells. We show that the N-terminal head domain is sufficient for DISC1 mitochondrial and nuclear targeting, while sequence from the C-terminus facilitates centrosomal association. Loss of C-terminal sequence alters DISC1 subcellular distribution, significantly increasing nuclear localization. DISC1 over-expression produces striking mitochondrial reorganization in some cells, with formation of mitochondrial ring-like structures, indicating a potential involvement of DISC1 in mitochondrial fusion and/or fission.