title: Ulk1-mediated Atg5-independent macroautophagy mediates elimination of mitochondria from embryonic reticulocytes.
abstract: 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.
authors.affiliation: Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Honda
authors.affiliation: Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Arakawa
authors.affiliation: Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Nishida
authors.affiliation: Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamaguchi
authors.affiliation: Department of Pediatrics, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishii
authors.affiliation: Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Shigeomi
authors.initials: S
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics*; D000071187:Autophagy-Related Protein 5; D000071189:Autophagy-Related Protein-1 Homolog; D002454:Cell Differentiation; D004920:Erythropoiesis / Q000235:genetics*; D005333:Fetus / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012156:Reticulocytes / Q000378:metabolism*
chemical_list: C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; C112444:Ulk1 protein, mouse