Figure 1.

Mitochondrial ultrastructural changes in heart failure. (A) Transmission electron micrograph of longitudinal section of left ventricular (LV) myocardium suggests that each intermyofibrillar mitochondrion extends from one Z band to another, and neighbors with adjacent sarcomeres. The T-tubules (T), which are invaginations of the plasma membrane, are surrounded by the junctional sarcoplasmic reticulum (JSR), and are interspersed between adjacent intermyofibrillar mitochondria. The longitudinal sarco/endoplasmic reticulum runs in a network configuration between adjacent intermyofibrillar mitochondria and sarcomeres. This topology of the intermyofibrillar mitochondria places them at the hub of calcium signaling by being physically tethered and functionally coupled with the adjacent organelles, particularly the endoplasmic reticulum. Photomicrograph is 40k X magnified, scale bar 0.5 μm. (B) Transmission electron micrograph of LV myocardium in systolic HF (HFrEF). Please refer to text in the body of manuscript for details. Yellow circles showing areas where lysosomes are fusing with surrounding mitochondria. Blue asterisks showing mitochondria at different stages of vacuolar degeneration. Additionally, there is accumulation of lipid (L) particles in the cytoplasm in heart failure (HF) myocardium. Very few lipid particles are seen in normal myocardium. Images are 5k, 12k, 20k and 40k X magnified, scale bar 2 μm, 1 μm, 1 μm and 0.5 μm, respectively. IMF: intermyofibrillar mitochondria, JSR: junctional sarcoplasmic reticulum, T: T-tubule. Figure 1A is adapted and modified with permission from Stem Cell and Gene Therapy for Cardiovascular Disease (2016), Chapter 30, Chaanine et al.