Fig. 9: Loss of PINK1 or Parkin leads to dysregulation of ER and cytosolic calcium homeostasis. | Nature Communications

Fig. 9: Loss of PINK1 or Parkin leads to dysregulation of ER and cytosolic calcium homeostasis.

From: PINK1 and Parkin regulate IP3R-mediated ER calcium release

Fig. 9

a In normal conditions, PINK1 activates the Parkin E3 ligase that results in ubiquitination and degradation of CISD1, located on the outer mitochondrial membrane. As CISD1 normally activates the ER calcium channel IP3R, inhibition of CISD1 by Parkin leads to suppressed IP3R activity and decreased cytosolic calcium levels. b However, in PD conditions induced by PINK1 or Parkin mutations, increased CISD1 protein levels cause elevated IP3R activity and cytosolic calcium levels. The inhibitor of CISD1 pioglitazone suppresses IP3R activity and restores calcium homeostasis, and therefore rescues the PD phenotypes caused by loss of PINK1 or Parkin. This figure was created with images from BioRender.com.

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