Figure 7.

Schematic diagram of DIMT1-mediated β-cell dysfunction. Deficiency of DIMT1 may lead to attenuation of cellular protein synthesis and mitochondrial dysfunction, which both contribute to the pathogenesis of T2D. 18S rRNA methylation by DIMT1 is instrumental in rRNA processing and protein translation. In the event this is perturbed, translation of proteins required for mitochondrial functions, such as OXPHOS, ATP production and ΔΨm, is impacted. Consequently, mitochondrial dysfunction causes defects in insulin secretion that lead to hyperglycemia. In parallel, deficiency of DIMT1 leads to rRNA processing defects and also to an interference of the interaction between NOB-1 and PES-1. This interaction is crucial for late rRNA maturation and efficient translation, which, when hindered, may lead to further perturbation in overall protein synthesis. Attenuation of cellular protein synthesis is likely to impact insulin content, which contributes to the hyperglycemic condition. ΔΨm, mitochondrial membrane potential; ATP, adenosine triphosphate; NOB-1, NIN1 (RPN12) binding protein 1 Homolog; OXPHOS, mitochondrial oxidative phosphorylation; PES-1, pescadillo ribosomal biogenesis factor 1; rRNA, ribosomal RNA.