Autophagy-dependent and -independent mechanisms of mitochondrial clearance during reticulocyte maturation.
Autophagy-dependent and -independent mechanisms of mitochondrial clearance during reticulocyte maturation.
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DOI：
10.4161/auto.5.7.9749
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发表时间：
2009-10
期刊：
影响因子：
13.3
通讯作者：
Ney PA
中科院分区：
文献类型：
--
作者：
Zhang J;Ney PA
红细胞的形成涉及网织红细胞发育阶段线粒体的消除。NIX−/−网织红细胞在这一步未能消除其线粒体，原因是线粒体对自噬小体的靶向存在缺陷。为了确定自噬在这一过程中的作用，我们建立了ATG7−/−移植小鼠。ATG7−/−网织红细胞存在线粒体清除的部分缺陷，说明线粒体清除存在自噬依赖和非依赖机制。我们使用ATG7−/−自噬缺陷网织红细胞来研究线粒体清除的时间事件。线粒体去极化先于消除，但在−/−网织红细胞中，去极化事件明显延迟。由于ATG7调节自噬小体的形成，我们推测网织红细胞中线粒体的去极化发生在自噬小体形成的下游。我们认为线粒体清除有两种机制：一种是由线粒体去极化触发的，另一种是NIX依赖的机制，而不是。Nix依赖的机制仍有待阐明。
Erythrocyte formation involves the elimination of mitochondria at the reticulocyte stage of development. Nix−/− reticulocytes fail to eliminate their mitochondria at this step due to a defect in the targeting of mitochondria to autophagosomes. To determine the role of autophagy in this process, we generated Atg7−/− transplant mice. Atg7−/− reticulocytes exhibit a partial defect in mitochondrial clearance, demonstrating that there are both autophagy-dependent and -independent mechanisms of mitochondrial clearance. We used Atg7−/− autophagy-defective reticulocytes to study temporal events in mitochondrial clearance. Mitochondrial depolarization precedes elimination, but in Atg7−/− reticulocytes the depolarization event is markedly delayed. Since Atg7 regulates autophagosome formation, we infer that mitochondrial depolarization occurs downstream of autophagosome formation in reticulocytes. We propose that there are two mechanisms of mitochondrial clearance: one that is triggered by mitochondrial depolarization, and a second NIX-dependent mechanism, which is not. The NIX-dependent mechanism remains to be elucidated.