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Blood, 15 August 2008, Vol. 112, No. 4, pp. 1493-1502.
Prepublished online as a Blood First Edition Paper on June 6, 2008; DOI 10.1182/blood-2008-02-137398.
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Submitted February 4, 2008
Accepted May 6, 2008
Ulk1 plays a critical role in the autophagic clearance of mitochondria and ribosomes during reticulocyte maturation
Mondira Kundu*, Tullia Lindsten, Chia-Ying Yang, Junmin Wu, Fangping Zhao, Ji Zhang, Mary A Selak, Paul A Ney, and Craig B Thompson
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States
Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, United States
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, United States
Department of Pediatrics, Children's Hospital and University of Pennsylvania, Philadelphia, PA, United States
Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA, United States
* Corresponding author; email: kundum{at}uphs.upenn.edu.
Production of a red blood cell's hemoglobin depends on mitochondrial heme synthesis. However, mature red blood cells are devoid of mitochondria and rely on glycolysis for ATP production. The molecular basis for the selective elimination of mitochondria from mature red blood cells remains controversial. Recent evidence suggests that clearance of both mitochondria and ribosomes, which occurs in reticulocytes following nuclear extrusion, depends on autophagy. Here, we demonstrate that Ulk1, a serine threonine kinase with homology to yeast atg1p, is a critical regulator of mitochondrial and ribosomal clearance during the final stages of erythroid maturation. However, in contrast to the core autophagy genes such as atg5 and atg7, expression of ulk1 is not essential for induction of macroautophagy in response to nutrient deprivation or for survival of newborn mice. Together, these data suggest that the ATG1 homologue, Ulk1, is a component of the selective autophagy machinery that leads to the elimination of organelles in erythroid cells rather that an essential mechanistic component of autophagy.

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