ER membranes associated with mitochondria: Possible therapeutic targets in heart-associated diseases

Pharmacol Res. 2020 Jun;156:104758. doi: 10.1016/j.phrs.2020.104758. Epub 2020 Mar 18.


Cardiovascular system cell biology is tightly regulated and mitochondria play a relevant role in maintaining heart function. In recent decades, associations between such organelles and the sarco/endoplasmic reticulum (SR) have been raised great interest. Formally identified as mitochondria-associated SR membranes (MAMs), these structures regulate different cellular functions, including calcium management, lipid metabolism, autophagy, oxidative stress, and management of unfolded proteins. In this review, we highlight MAMs' alterations mainly in cardiomyocytes, linked with cardiovascular diseases, such as cardiac ischemia-reperfusion, heart failure, and dilated cardiomyopathy. We also describe proteins that are part of the MAMs' machinery, as the FUN14 domain containing 1 (FUNDC1), the sigma 1 receptor (Sig-1R) and others, which might be new molecular targets to preserve the function and structure of the heart in such diseases. Understanding the machinery of MAMs and its function demands our attention, as such knowledge might contribute to strengthen the role of these relative novel structures in heart diseases.

Keywords: Cardiomyocytes; Cardiovascular diseases; Endoplasmic reticulum; MAMs; Mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium Signaling
  • Cardiovascular Agents / therapeutic use
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum / pathology
  • Heart Diseases / drug therapy
  • Heart Diseases / metabolism*
  • Heart Diseases / pathology
  • Heart Diseases / physiopathology
  • Humans
  • Membrane Proteins / metabolism
  • Mitochondria, Heart / drug effects
  • Mitochondria, Heart / metabolism*
  • Mitochondria, Heart / pathology
  • Mitochondrial Membranes / drug effects
  • Mitochondrial Membranes / metabolism*
  • Mitochondrial Membranes / pathology
  • Mitochondrial Proteins / metabolism
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Receptors, sigma / metabolism


  • Cardiovascular Agents
  • FUNDC1 protein, human
  • Membrane Proteins
  • Mitochondrial Proteins
  • Receptors, sigma
  • sigma-1 receptor