Organelles Stress and their Crosstalk within Diabetic Myocardium

Diabetes-associated cardiovascular dysfunction is characterized by homeostasis perturbation induced by systemic stressors, such as hyperglycemia, excess of reactive oxygen and nitrogen species, shear-stress, and inflammatory environment. The recent data highlight the aggravating effect of local, organelles-related stress, manifest in mitochondria, endoplasmic reticulum (ER), lysosomes, proteasomes, inflammasomes. The occurrence of local stress might allow its alleviation inside the cell, at organelles level, a novel strategy potentially more efficient compared to current systemic therapeutic approaches. The aim of this article is to link the electron microscopy evidence on mitochondrial stress in diabetic coronary endothelium and cardiomyocytes (CMs) to the newly identified molecules/ mechanisms beyond it. The issues examined are: (i) Mitochondrial homeostasis and "quality control" mechanisms within myocardium, (ii) Mitochondrial dysfunction and dynamics within diabetic myocardium: fusion, fission, and mitophagy events, (iii) The molecular crosstalk between mitochondria, ER, lipid droplets, and cytoplasm, (iv) Perspectives. At the horizon, targeting mitochondrial dynamics mediators, deciphering the defects in mitochondrial cell signaling control, understanding mitochondria retrograde signaling, and manipulation of ER stress-associated lipid droplets formation may conduct to novel drugs aimed to preserve CMs viability and to alleviate diabetesinduced heart damage.