Mitochondrial clearance by autophagy in developing erythrocytes: Clearly important, but just how much so?

Nuffield Department of Medicine, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
Cell cycle (Georgetown, Tex.) (Impact Factor: 4.57). 05/2010; 9(10):1901-6. DOI: 10.4161/cc.9.10.11603
Source: PubMed


Erythrocytes are anucleated cells devoid of organelles. Expulsion of the nucleus from erythroblasts leads to the formation of reticulocytes, which still contain organelles. The mechanisms responsible for the final removal of organelles from developing erythroid cells are still being elucidated. Mitochondria are the most abundant organelles to be cleared for the completion of erythropoiesis. Macroautophagy, referred to as autophagy, is a regulated catabolic pathway consisting of the engulfment of cytoplasmic cargo by a double membraned-vesicle, the autophagosome, which typically then fuses to lysosomal compartments for the degradation of the sequestered material. Early electron microscopic observations of reticulocytes suggested the autophagic engulfment of mitochondria (mitophagy) as a possible mechanism for mitochondrial clearance in these. Recently, a number of studies have backed this hypothesis with molecular evidence. Indeed, the absence of Nix, which targets mitochondria to autophagosomes, or the deficiency of proteins in the autophagic pathway lead to impaired mitochondrial clearance from developing erythroid cells. Importantly, however, the extent to which the absence of mitophagy affects erythroid development differs depending on the model and gene investigated. This review will therefore focus on comparing the different studies of mitophagy in erythroid development and highlight some of the remaining controversial points.

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    • "Nix was recently found to bind the mammalian LC3 and GABARAP and thus recruit forming autophagosomes to depolarized mitochondria. As such Nix may represent the closest mammalian homologue of the yeast Atg32, at least in erythroid mitophagy [80]. Figure 7. Schematic representation of the structure of p62 and NBR1 adaptors, and of their binding partners. "
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    • "Blocking caspase activation via inhibitors has been found to induce alternative cell death pathways such as autophagy or necrosis through an increased production of reactive oxygen species (ROS) [23]. Autophagic mechanisms are of particular importance in terminal differentiation stages of erythroid cells for the removal of mitochondria in so-called mitophagy [24], [25] and might become deregulated when concentrations of ROS are further increased and could thus explain the severe effect of SIT on late erythroblast and reticulocyte stages. "
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