MTOR-independent autophagy induced by interrupted endoplasmic reticulum-mitochondrial Ca2+ communication: a dead end in cancer cells
MTOR-independent autophagy induced by interrupted endoplasmic reticulum-mitochondrial Ca2+ communication: a dead end in cancer cells
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DOI：
10.1080/15548627.2018.1537769
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发表时间：
2019-02-01
期刊：
影响因子：
13.3
通讯作者：
Cardenas, Cesar
中科院分区：
文献类型：
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作者：
Ahumada-Castro, Ulises;Silva-Pavez, Eduardo;Cardenas, Cesar
内质网 (ER)-线粒体 Ca2+ 通讯的中断会引发生物能危机，其特征是不依赖 MTOR 的 AMPK 依赖的巨自噬/自噬通量增加，这不足以重建癌细胞中的代谢和能量稳态。在此，我们提出，在内质网线粒体 Ca2+ 转移抑制后，存在于线粒体相关膜 (MAM) 上的 AMPK 通过 BECN1 (beclin 1) 激活局部自噬。这种局部反应可能会阻止适当的细胞器间通讯，而细胞器间通讯将使自噬衍生的代谢物达到必要的合成代谢途径，以维持线粒体功能和细胞稳态。
The interruption of endoplasmic reticulum (ER)-mitochondrial Ca2+ communication induces a bioenergetic crisis characterized by an increase of MTOR-independent AMPK-dependent macroautophagic/autophagic flux, which is not sufficient to reestablish the metabolic and energetic homeostasis in cancer cells. Here, we propose that upon ER-mitochondrial Ca2+ transfer inhibition, AMPK present at the mitochondria-associated membranes (MAMs) activate localized autophagy via BECN1 (beclin 1). This local response could prevent the proper interorganelle communication that would allow the autophagy-derived metabolites to reach the necessary anabolic pathways to maintain mitochondrial function and cellular homeostasis.