Details

Autor(en) / Beteiligte

• Kerkhofs, Martijn
• Bultynck, Geert
• Vervliet, Tim
• Monaco, Giovanni

Titel

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

Ist Teil von

• Drug discovery today, 2019-05, Vol.24 (5), p.1092-1103

Ort / Verlag

Elsevier Ltd

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• •ER–mitochondria Ca2+ crosstalk is crucial for cell life or death.•In pathological conditions, the ER–mitochondria Ca2+-fluxes are often altered.•Novel peptide tools target the Ca2+-flux-PPI systems at the ER–mitochondria interface.•These peptides show promising results in vitro and in preclinical models of disease.•Advances in medicinal chemistry are determining their future development as therapeutics. 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. This review provides an up-to-date overview of the different peptides that have emerged as modulators of ER–mitochondrial Ca2+ fluxes with translational and therapeutic potential.