Type 2 diabetes (T2D) can be attributed to loss of β-cell identity or de-differentiation, marked by acquisition of immature cell markers and loss of insulin expression and secretion. While the etiology of β-cell immaturity in T2D is unclear, impairments in nuclear-encoded mitochondrial gene expression and transcription factor (TF) expression occur. Additionally, defects in mitochondrial structure and function leads to impaired glucose- stimulated insulin secretion (GSIS) and have been reported in β-cells of human T2D patients. Interestingly, the transcriptional changes that occur during β-cell immaturity involve loss of the nuclear-encoded mitochondrial gene expression program. My studies will test the hypothesis that β-cell immaturity in T2D is driven by loss of mitochondrial functional gene regulation by the TFs MAF bZIP transcription factor A (MAFA) or B (MAFB). Furthermore, I predict that MAFA/MAFB are themselves targets of mito-nuclear crosstalk through a retrograde signaling cascade induced by defects in mitochondrial function.