Table 2.
Consequences of TAZ mutations and subsequent tafazzin deficiency in multiple BTHS models.
| Model organism | General phenotype | Mitochondrial events |
|---|---|---|
| Yeast Saccharomyces cerevisiae | • Temperature-sensitive growth on a non-fermentable carbon source | •Abnormal morphology |
| • Partial uncoupling | ||
| • Reduced osmotic stability | ||
| •Increased oxidative stress ∗ | ||
| • Reduced stability of respiratory supercomplexes | ||
| • Disruption of iron homeostasis | ||
| Fly Drosophila melanogaster | • Flight muscle weakness | •Abnormal morphology of the flight muscle |
| • Defective spermatogenesis | ||
| • Inner membrane aggregation | ||
| • Reduced state-3 respiration | ||
| • Reduced dimerization and dimer row formation by ATP synthase | ||
| Zebrafish | • Early lethality | |
| Danio rerio | • Abnormal embryogenesis and cardiac development | |
| Mouse | • Prenatal and perinatal mortality | • Hyperproliferation of cardiac mitochondria |
| Mus musculus | • Low body weight | •Abnormal morphology |
| • Developmental cardiomyopathy | • Reduced crista density | |
| • Adult cardiomyopathy (dilated type) | • Disrupted alignment between mitochondria and myofibrils | |
| • Skeletal muscle weakness | ||
| Human | • Fetal loss and stillbirth | •Abnormal morphology |
| Homo sapiens | • Abnormal growth | • Inner membrane aggregation |
| • Chronic fatigue | • Smaller membrane potential (Δψm) | |
| • Cardiomyopathy | • Reduced state-3 respiration | |
| • Skeletal muscle weakness | • Reduced stability of the respiratory RCs | |
| • Neutropenia | • Slight increase in ROS production | |
| • Release of cytochrome c and stimulation of apoptosis in progenitor cells | ||
| • Resistance to Fas and TNFα-induced apoptosis | ||
| • Disrupted alignment between mitochondria and myofibrils | ||
Very important clues from the yeast cell model are shown in red, whereas shared characteristics are shown in blue. ∗Indicates essential discoveries taken into account in the recent work on human induced pluripotent stem cells (hiPSC).