# Cardiac SR-Mitochondria Contacts—Impact on Cardiac Physiology and Mitochondrial Fitness

## TL;DR

This review explores how the physical connections between the sarcoplasmic reticulum and mitochondria in heart cells are vital for heart function and mitochondrial health.

## Contribution

The paper compiles and analyzes proteins enriched in cardiac MAMs and their roles in cardiac physiology and disease.

## Key findings

- SR-mitochondria contact sites regulate lipid exchange, calcium communication, and ROS production in cardiomyocytes.
- Proteins like the mitochondrial Ca2+ uniporter and DRP1 are enriched in these contact sites and influence cardiac function.
- Mispositioning of these proteins may contribute to cardiac diseases.

## Abstract

In adult cardiomyocytes, within the Mitochondrial Associated Membranes (MAMs), the sarcoplasmic reticulum (SR) and mitochondria juxtapose each other, forming a unique and highly repetitive functional structure throughout the cells. These SR-mitochondria contact sites have emerged as critical structures that regulate various physiological processes, including lipid exchange, calcium (Ca2+) communication, control of excitation-contraction bioenergetics coupling, and reactive oxygen species (ROS) production. Over the years, several scientific studies have reported the accumulation of diverse proteins within these SR-mitochondria close contacts. Some proteins strategically accumulate in these areas to enhance their function, such as the mitochondrial Ca2+ uniporter, while others perform non-canonical roles, such as DRP1 acting as a bioenergetics regulator. The purpose of this review is to provide a comprehensive compilation of the proteins that have been reported to be enriched in cardiac MAMs. We aim to show how their positioning is crucial for proper cardiac physiology and fitness, as well as how mispositioning may contribute to cardiac diseases. Additionally, we will discuss the gaps in our understanding and identify the necessary components to fully comprehend physiological communication between the sarcoplasmic SR and mitochondria in cardiac tissue.