ROMO1 is essential for glucose coupling in the pancreatic β cell of male mice

Abstract Reactive oxygen species modulator 1 (ROMO1) is a highly conserved inner mitochondrial membrane protein that senses ROS and regulates mitochondrial dynamics 1 . ROMO1 is required for mitochondrial fusion in vitro , and silencing ROMO1 increases sensitivity to cell death stimuli. How ROMO1 promotes mitochondrial fusion and its physiological role remain unclear. Here we show that ROMO1 is essential for embryonic development, as ROMO1-null mice die before embryonic day 8.5, earlier than GTPases OPA1 or MFN1/2 that catalyze mitochondrial membrane fusion. Knockout of ROMO1 in adult pancreatic β cells results in impaired glucose homeostasis in male mice due to an insulin secretion defect resulting from impaired glucose sensing. Mitochondria in ROMO1 β cell KO cells were swollen and fragmented, consistent with a role for ROMO1 in mitochondrial fusion in vivo . While basal respiration was normal in ROMO1β cell KO islets, spare respiratory capacity was lost. Taken together, our data indicate that ROMO1 is required for nutrient coupling in the β cell and point to a critical role for spare respiratory capacity in the maintenance of euglycemia in males.