OGT Regulates Mitochondrial Biogenesis and Function via Diabetes Susceptibility Gene Pdx1

Ramkumar Mohan, Seokwon Jo, Amber Lockridge, Deborah A. Ferrington, Kevin Murray, Arthur Eschenlauer, Ernesto Bernal-Mizrachi, Yoshio Fujitani, Emilyn U. Alejandro

Research output: Contribution to journalArticlepeer-review


O-GlcNAc transferase (OGT), a nutrient sensor sensitive to glucose flux, is highly expressed in the pancreas. However, the role of OGT in the mitochondria of β-cells is unexplored. In this study, we identified the role of OGT in mitochondrial function in β-cells. Constitutive deletion of OGT (βOGTKO) or inducible ablation in mature β-cells (iβOGTKO) causes distinct effects on mitochondrial morphology and function. Islets from βOGTKO, but not iβOGTKO, mice display swollen mitochondria, reduced glucose-stimulated oxygen consumption rate, ATP production, and glycolysis. Alleviating endoplasmic reticulum stress by genetic deletion of Chop did not rescue the mitochondrial dysfunction in βOGTKO mice. We identified altered islet proteome between βOGTKO and iβOGTKO mice. Pancreatic and duodenal homeobox 1 (Pdx1) was reduced in in βOGTKO islets. Pdx1 overexpression increased insulin content and improved mitochondrial morphology and function in βOGTKO islets. These data underscore the essential role of OGT in regulating β-cell mitochondrial morphology and bioenergetics. In conclusion, OGT couples nutrient signal and mitochondrial function to promote normal β-cell physiology.

Original languageEnglish (US)
Pages (from-to)2608-2625
Number of pages18
Issue number11
StatePublished - Nov 1 2021

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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