Disrupted in Schizophrenia 1 (DISC1) is a multicompartmentalized protein that predominantly localizes to mitochondria

Abstract

DISC1 is disrupted by a chromosomal translocation cosegregating with schizophrenia and recurrent major depression in a large Scottish family and has also been reported as a potential susceptibility locus in independent populations. We reveal a widespread and complex pattern of DISC1 expression, with at least five forms of Disrupted in Schizophrenia 1 DISC1 detectable. Mitochondria are the predominant site of DISC1 expression with additional nuclear, cytoplasmic, and actin-associated locations evident. Although the subcellular targeting of DISC1 is clearly complex, the association with mitochondria is of interest as many mitochondrial deficits have been reported in schizophrenia and other neuropsychiatric illnesses. Moreover, of the many cellular functions performed by mitochondria, their role in oxidative phosphorylation, calcium homeostasis, and apoptosis may hold particular relevance for the neuronal disturbances believed to be involved in the pathogenesis of schizophrenia.