Autophagy of mitochondria in rat bone marrow erythroid cells Relation to nuclear extrusion

Heynen, M. J.; Tricot, Guido; Verwilghen, R. L.

doi:10.1007/bf00214924

Cited by 57 publications

(48 citation statements)

References 12 publications

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“…At this stage the autophagic process contributes to the removal of mitochondria. 14 In rat studies, autophagosomes occupied 0.2% of the cytoplasm of differentiated erythroblasts, 15 which is consistent with the results of this study. In MDS erythroblasts, however, this fraction is approximately five times higher.…”

Section: Discussionsupporting

confidence: 89%

Erythroid precursors from patients with low-risk myelodysplasia demonstrate ultrastructural features of enhanced autophagy of mitochondria

et al. 2009

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Recent studies in erythroid cells have shown that autophagy is an important process for the physiological clearance of mitochondria during terminal differentiation. However, autophagy also plays an important role in removing damaged and dysfunctional mitochondria. Defective mitochondria and impaired erythroid maturation are important characteristics of low-risk myelodysplasia. In this study we therefore questioned whether the autophagic clearance of mitochondria might be altered in erythroblasts from patients with refractory anemia (RA, n ¼ 3) and RA with ringed sideroblasts (RARS, n ¼ 6). Ultrastructurally, abnormal and iron-laden mitochondria were abundant, especially in RARS patients. A large proportion (52±16%) of immature and mature myelodysplastic syndrome (MDS) erythroblasts contained cytoplasmic vacuoles, partly double membraned and positive for lysosomal marker LAMP-2 and mitochondrial markers, findings compatible with autophagic removal of dysfunctional mitochondria. In healthy controls only mature erythroblasts comprised these vacuoles (12 ± 3%). These findings were confirmed morphometrically showing an increased vacuolar surface in MDS erythroblasts compared to controls (Po0.0001). In summary, these data indicate that MDS erythroblasts show features of enhanced autophagy at an earlier stage of erythroid differentiation than in normal controls. The enhanced autophagy might be a cell protective mechanism to remove defective iron-laden mitochondria.

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Section: Discussionsupporting

confidence: 89%

Erythroid precursors from patients with low-risk myelodysplasia demonstrate ultrastructural features of enhanced autophagy of mitochondria

et al. 2009

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“…15 Therefore, we examined the effect of NIX deficiency on the induction of autophagy during terminal erythroid differentiation. Autophagy was induced during terminal erythroid differentiation, as shown by the conversion of LC3, a mammalian homolog of Atg8, from its unmodified form (LC3-I) to its lipid-modified form (LC3-II).…”

Section: Nix Is Required For Mitochondrial Autophagymentioning

confidence: 99%

“…2 Mitochondrial clearance from reticulocytes occurs through an autophagy-related process. 15 Consequently, reticulocytes provide a physiological model of mitochondrial autophagy and its regulation by a Bcl-2-related protein.…”

Section: Introductionmentioning

confidence: 99%

NIX induces mitochondrial autophagy in reticulocytes

Zhang¹,

Ney²

2008

Autophagy

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The controlled elimination of defective mitochondria is necessary for the health of long-lived post-mitotic cells, like cardiomyocytes and neurons. Mitochondrial elimination also occurs during the course of normal development, in lens epithelial and erythroid cells. Strikingly, at the final stage of erythroid cell maturation, newly formed erythrocytes, also known as reticulocytes, eliminate their entire cohort of mitochondria. We have employed this model to investigate the mechanism of programmed mitochondrial clearance. NIX (BNIP3L) is a Bcl-2-related protein that is upregulated during terminal erythroid differentiation. 1,2 NIX-deficient reticulocytes have a significant defect of mitochondrial clearance. Consistent with the ability of NIX to cause mitochondrial depolarization, 3,4 we show that mitochondria are depolarized in wild type but not NIX deficient reticulocytes. NIX does not function through established proapoptotic pathways, nor does it mediate the induction of autophagy in erythroid cells. Rather, NIX is required for the selective incorporation of mitochondria into autophagosomes. Elucidation of the mechanism of this effect will improve our understanding of the role of autophagy in the maintenance of cellular homeostasis.

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“…During erythrocyte maturation, the erythroblasts lose their nuclei to become reticulocytes, which are transformed into erythrocytes (EC) by the elimination of organelles, including the mitochondria. It is believed that macroautophagy is involved in this process because ultrastructural studies have detected autophagic structures engulfing mitochondria 14,15 . The involvement of Atg5 and Atg7 remains controversial due to conflicting reports [16][17][18] .…”

mentioning

confidence: 99%

Ulk1-mediated Atg5-independent macroautophagy mediates elimination of mitochondria from embryonic reticulocytes

et al. 2014

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Macroautophagy is a highly conserved intracellular process responsible for the degradation of subcellular constituents. Macroautophagy was recently suggested to be involved in the removal of mitochondria from reticulocytes during the final stage of erythrocyte differentiation. Although Atg5 and Atg7 are indispensable for macroautophagy, their role in mitochondrial clearance remains controversial. We recently discovered that mammalian cells use conventional Atg5/Atg7-dependent macroautophagy as well as an alternative Unc-51-like kinase 1 (Ulk1)-dependent Atg5/Atg7-independent macroautophagy process. We hypothesized that the latter may be involved in mitochondrial clearance from reticulocytes during erythrocyte differentiation. Here we report that fetal definitive reticulocytes from Ulk1-deficient and Ulk1/Atg5 double-deficient mice retain their mitochondria, whereas the mitochondria are engulfed and digested within autophagic structures in wild-type and Atg5-deficient mice. Mitochondrial retention by Ulk1-deficient reticulocytes is far less marked in primitive and adult definitive reticulocytes. These data indicate that Ulk1-dependent Atg5-independent macroautophagy is the dominant process of mitochondrial clearance from fetal definitive reticulocytes.

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Autophagy of mitochondria in rat bone marrow erythroid cells Relation to nuclear extrusion

Cited by 57 publications

References 12 publications

Erythroid precursors from patients with low-risk myelodysplasia demonstrate ultrastructural features of enhanced autophagy of mitochondria

Erythroid precursors from patients with low-risk myelodysplasia demonstrate ultrastructural features of enhanced autophagy of mitochondria

NIX induces mitochondrial autophagy in reticulocytes

Ulk1-mediated Atg5-independent macroautophagy mediates elimination of mitochondria from embryonic reticulocytes

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