Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Department of Pediatrics, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.
Nat Commun. 2014 Jun 4;5:4004. doi: 10.1038/ncomms5004.
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.
自噬是一种高度保守的细胞内过程，负责降解细胞内成分。最近有研究表明，自噬可能参与网织红细胞在红细胞分化的最后阶段中线粒体的去除。虽然 Atg5 和 Atg7 对自噬是不可或缺的，但它们在清除线粒体中的作用仍存在争议。我们最近发现哺乳动物细胞使用传统的 Atg5/Atg7 依赖性自噬以及替代的 Unc-51 样激酶 1（Ulk1）依赖性 Atg5/Atg7 非依赖性自噬过程。我们假设后者可能参与红细胞分化过程中网织红细胞中线粒体的清除。在这里，我们报告说，Ulk1 缺陷型和 Ulk1/Atg5 双缺陷型小鼠的胎儿期定型网织红细胞保留其线粒体，而在野生型和 Atg5 缺陷型小鼠中，线粒体被吞噬并在自噬结构中消化。Ulk1 缺陷型网织红细胞中保留的线粒体在原始和成年定型网织红细胞中要少得多。这些数据表明，Ulk1 依赖性、Atg5 非依赖性自噬是胎儿定型网织红细胞中线粒体清除的主要过程。
