Therapeutic implications of novel peptides targeting ER-mitochondria Ca2+-flux systems.

Intracellular Ca2+-flux systems located at the ER-mitochondrial axis govern mitochondrial Ca2+ balance and cell fate. Multiple yet incurable pathologies are characterized by insufficient or excessive Ca2+ fluxes toward the mitochondria, in turn leading to aberrant cell life or death dynamics. The discovery and ongoing molecular characterization of the main interorganellar Ca2+ gateways have resulted in a novel class of peptide tools able to regulate relevant protein-protein interactions (PPIs) underlying this signaling scenario. Here, we review peptides, molecularly derived from Ca2+-flux systems or their accessory proteins. We discuss how they alter Ca2+-signaling protein complexes and modulate cell survival in light of their forthcoming therapeutic applications.