Targeting Calcium-Mediated Inter-Organellar Crosstalk in Cardiac Diseases

Authors

Mohit M Hulsurkar
Satadru K Lahiri
Jason Karch
Meng C Wang
Xander H T Wehrens

Publication Date

4-1-2022

Journal

Expert Opinion on Therapeutic Targets

DOI

10.1080/14728222.2022.2067479

PMID

35426759

PMCID

PMC9081256

PubMedCentral® Posted Date

4-25-2023

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Calcium, Calcium Signaling, Heart Diseases, Humans, Myocytes, Cardiac, Ryanodine Receptor Calcium Release Channel, Sarcoplasmic Reticulum

Abstract

INTRODUCTION: Abnormal calcium signaling between organelles such as the sarcoplasmic reticulum (SR), mitochondria and lysosomes is a key feature of heart diseases. Calcium serves as a secondary messenger mediating inter-organellar crosstalk, essential for maintaining the cardiomyocyte function.

AREAS COVERED: This article examines the available literature related to calcium channels and transporters involved in inter-organellar calcium signaling. The SR calcium-release channels ryanodine receptor type-2 (RyR2) and inositol 1,4,5-trisphosphate receptor (IP

EXPERT OPINION: Enhanced SR calcium release via RyR2 and reduced SR reuptake via SERCA2a, increased VDAC and MCUC-mediated calcium uptake into mitochondria, and enhanced lysosomal calcium-release via lysosomal TPC and TRPML may all contribute to aberrant calcium homeostasis causing heart disease. While mechanisms of this crosstalk need to be studied further, interventions targeting these calcium channels or combinations thereof might represent a promising therapeutic strategy.