Effects of the novel mitochondrial protein mimitin in insulin-secreting cells

Abstract

Mimitin, a novel mitochondrial protein, has been shown to act as a molecular chaperone for the mitochondrial complex I and to regulate ATP synthesis. During Type 1 diabetes development, pro-inflammatory cytokines induce mitochondrial damage in pancreatic β-cells, inhibit ATP synthesis and reduce glucose-induced insulin secretion. Mimitin was expressed in rat pancreatic islets including β-cells and decreased by cytokines. In the ob/ob mouse, a model of insulin resistance and obesity, mimitin expression was down-regulated in liver and brain, up-regulated in heart and kidney, but not affected in islets. To further analyse the impact of mimitin on β-cell function, two β-cell lines, one with a low (INS1E) and another with a higher (MIN6) mimitin expression were studied. Mimitin overexpression protected INS1E cells against cytokine-induced caspase 3 activation, mitochondrial membrane potential reduction and ATP production inhibition, independently from the NF-κB (nuclear factor κB)-iNOS (inducible NO synthase) pathway. Mimitin overexpression increased basal and glucose-induced insulin secretion and prevented cytokine-mediated suppression of insulin secretion. Mimitin knockdown in MIN6 cells had opposite effects to those observed after overexpression. Thus mimitin has the capacity to modulate pancreatic islet function and to reduce cytokine toxicity.