Secretory pathway Ca²⁺-ATPase SPCA2 regulates mitochondrial respiration and DNA damage response through store-independent calcium entry.

ABSTRACT: A complex interplay between the extracellular space, cytoplasm and individual organelles modulates Ca²⁺ signaling to impact all aspects of cell fate and function. In recent years, the molecular machinery linking endoplasmic reticulum stores to plasma membrane Ca²⁺ entry has been defined. However, the mechanism and pathophysiological relevance of store-independent modes of Ca²⁺ entry remain poorly understood. Here, we describe how the secretory pathway Ca²⁺-ATPase SPCA2 promotes cell cycle progression and survival by activating store-independent Ca²⁺ entry through plasma membrane Orai1 channels in mammary epithelial cells. Silencing SPCA2 expression or briefly removing extracellular Ca²⁺ increased mitochondrial ROS production

SUBMITTER: Makena MR 

PROVIDER: S-EPMC8783100 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature