CISD2 ensures adequate ER-mitochondrial coupling, critically supporting mitochondrial function in neurons.

ABSTRACT: Loss of Cisd2, an iron-sulfur cluster transfer protein, results in type 2 Wolfram syndrome (WS2), a disorder associated with severe impacts on pancreatic β cell and neuronal functions. Cisd2 has been implicated in regulating intracellular Ca²⁺ signaling. However, the molecular basis and cellular consequences remain poorly understood. In this work, we demonstrate that Cisd2 intersects with intracellular Ca²⁺ dynamics at different levels, by interacting with the inositol-1,4,5-trisphosphate receptors and as a regulator of ER-mitochondria tethering. As such, loss of Cisd2 in HeLa cells results in reduced ER-mitochondrial Ca²⁺ transfer while only modestly impacting cytosolic Ca²⁺ signaling. In HeLa cells, Cisd2 deficiency promotes autophagic flux, ye

SUBMITTER: Loncke J 

PROVIDER: S-EPMC12659354 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature