Ca2+ imbalance caused by ERdj5 deletion affects mitochondrial fragmentation

Sci Rep. 2021 Nov 2;11(1):20772. doi: 10.1038/s41598-021-99980-9.


The endoplasmic reticulum (ER) is the organelle responsible for the folding of secretory/membrane proteins and acts as a dynamic calcium ion (Ca2+) store involved in various cellular signalling pathways. Previously, we reported that the ER-resident disulfide reductase ERdj5 is involved in the ER-associated degradation (ERAD) of misfolded proteins in the ER and the activation of SERCA2b, a Ca2+ pump on the ER membrane. These results highlighted the importance of the regulation of redox activity in both Ca2+ and protein homeostasis in the ER. Here, we show that the deletion of ERdj5 causes an imbalance in intracellular Ca2+ homeostasis, the activation of Drp1, a cytosolic GTPase involved in mitochondrial fission, and finally the aberrant fragmentation of mitochondria, which affects cell viability as well as phenotype with features of cellular senescence. Thus, ERdj5-mediated regulation of intracellular Ca2+ is essential for the maintenance of mitochondrial homeostasis involved in cellular senescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum-Associated Degradation
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Membrane Proteins
  • Mice
  • Mitochondria / pathology*
  • Protein Disulfide-Isomerases / genetics
  • Protein Disulfide-Isomerases / metabolism*


  • Membrane Proteins
  • Protein Disulfide-Isomerases
  • Calcium