Annexin A5 controls VDAC1-dependent mitochondrial Ca²⁺ homeostasis and determines cellular susceptibility to apoptosis.

ABSTRACT: Annexin A5 (AnxA5) is a Ca²⁺-dependent phospholipid-binding protein associated with the regulation of intracellular Ca²⁺ homeostasis. However, the precise role of AnxA5 in controlling mitochondrial Ca²⁺ signaling remains elusive. Here, we introduce a novel function of AnxA5 in regulating mitochondrial Ca²⁺ signaling. Our investigation revealed that AnxA5 localizes at and in the mitochondria and orchestrates intermembrane space Ca²⁺ signaling upon high Ca²⁺ elevations induced by ER Ca²⁺ release. Proximity ligation assays and co-immunoprecipitation revealed a close association but no direct contact of AnxA5 with the voltage-dependent anion channel (VDAC1) in the outer mitochondrial membrane (OMM). In single-cell mit

SUBMITTER: Oflaz FE 

PROVIDER: S-EPMC12170872 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature