We previously used transcriptional profiling to discover that the common form of type 2 diabetes mellitus is characterized by a gradual decline in the expression and activity of mitochondrial oxidative phosphorylation (OXPHOS).  This “mitochondrial signature” is subtle at the level of individual genes and could not have been detected using traditional experimental or analytical strategies focused on single genes.  The changes are concordant across scores of mitochondrial genes, and hence, statistically robust and likely biologically meaningful.  Our work has been corroborated by other groups and has contributed to the “mitochondrial hypothesis” for type 2 diabetes.  We are collaborating with leading human geneticists to determine if genetic variation in OXPHOS components or its regulatory machinery contribute to the inherited risk of developing type 2 diabetes mellitus.