@article{23148,
  abstract     = {Presenilin-1 (PS1) is an endoplasmic reticulum protein, most known for its role in pathogenesis of familial Alzheimer’s Disease (AD). PS1 has been attributed roles in intracellular calcium homeostasis in the brain, as well as in the pancreatic beta cells, where it has been shown to be fundamental for the initial phase of glucose-induced insulin secretion. To gain mechanistic insight into beta cell autonomous function of PS1, we have examined various beta cell models and found that PS1 controls glycolytic flux of pancreatic beta cells by regulating sub-mitochondrial Ca2+ homeostasis. Transient knock down of PS1 yielded a glycolytic bottleneck at the step catalyzed by glyceraldehyde-3-phosphate dehydrogenase, resulting in defective glucose responsiveness. Moreover, we show that PS1 is needed for the preservation of beta cell identity, likely due to its role in glycolysis. Finally, we show that mouse islets from an in vivo model of AD mimic the defective glucose responsiveness seen in beta cells with transient PS1 knock down, while the identity loss and whole-body glucose homeostasis are not severely impacted, suggesting an adaptive response. Thus, the current work highlights beta cell autonomous role of PS1 and adds a layer of complexity in its impact on whole body metabolism.},
  author       = {Koshenov, Zhanat and Postic, Sandra and Schoiswohl, Gabriela and Van Amsterdam, Savina and Hois-Zelinka, Victoria and Oflaz, Furkan E. and Rost, Rene and Tiapko, Oleksandra and Gottschalk, Benjamin and Hirtl, Martin and Bachkoenig, Olaf G. and Koshenova, Aigerim and Erdogan, Yusuf C. and Sagintayev, Adlet and Krnjic, Anita and Pfabe, Johannes U. and Sarikas, Srdjan and Hochreiter, Bernhard and Gindlhuber, Juergen and Schittmayer, Matthias and Tadic, Jelena and Ehall, Barbara and Madeo, Frank and Madl, Tobias and Malli, Roland and Birner-Gruenberger, Ruth and Pieber, Thomas and Eisenberg, Tobias and Slak Rupnik, Marjan and Graier, Wolfgang F.},
  issn         = {2399-3642},
  journal      = {Communications Biology},
  publisher    = {Springer Nature},
  title        = {{Presenilin-1 controls glycolysis and identity of pancreatic beta cells}},
  doi          = {10.1038/s42003-026-10581-6},
  volume       = {9},
  year         = {2026},
}