Autophagy in embryonic erythroid cells: its role in maturation

Yolk sac-derived embryonic erythroid cells differentiate synchronously in t he peripheral blood of Syrian hamster. The stage of differentiation on day 10 of gestation is equivalent to polychromatophilic erythroblast stage and that on day 13 is equivalent to the reticulocyte stage in adult animals. Th e cytoplasm of embryonic erythroid cells became scant and devoid of most or ganelles on day 12 of gestation. In addition, there were very few non-eryth roid cells in circulation before day 13. Thus the embryonic erythroid cells serve a pure and synchronous system to study the mechanisms of terminal di fferentiation. The number of mitochondria in the embryonic erythroid cells decreased to about 10% of the initial number during the period between day 10 and day 12 of gestation. In contrast, the frequency of autophagy of mito chondria increased 4.6-fold in the same period. The cytochrome c content of the cell decreased as the mitochondria became extinct. However, release of cytochrome c into the cytoplasm was not detectable through day 10 - 13 of gestation, suggesting that the mitochondria were digested within a closed c ompartment. Decomposed mitochondria and ferritin particles were detected in lysosomes by electron microscopy on and after day 12 of gestation, which a lso suggested digestion in a closed compartment, Mitochondrial ATP synthase subunit c, which is known to be a protease-refractory protein, was retaine d in the cells even after the disappearance of mitochondria, indicating tha t most of the mitochondria were not extruded from the cells. The digestion of mitochondria in autolysosomes may allow the cells to escape from rapid a poptotic cell death through concomitant removal of mitochondrial death-prom oting factors such as cytochrome c.