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Autophagy compensates for defects in mitochondrial dynamics

机译：自噬可补偿线粒体动态的缺陷

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Compromising mitochondrial fusion or fission disrupts cellular homeostasis; however, the underlying mechanism(s) are not fully understood. The loss of C . elegans fzo-1 ~(MFN) results in mitochondrial fragmentation, decreased mitochondrial membrane potential and the induction of the mitochondrial unfolded protein response (UPR ~(mt)). We performed a genome-wide RNAi screen for genes that when knocked-down suppress fzo-1 ~(MFN)(lf)-induced UPR ~(mt). Of the 299 genes identified, 143 encode negative regulators of autophagy, many of which have previously not been implicated in this cellular quality control mechanism. We present evidence that increased autophagic flux suppresses fzo-1 ~(MFN)(lf)-induced UPR ~(mt) by increasing mitochondrial membrane potential rather than restoring mitochondrial morphology. Furthermore, we demonstrate that increased autophagic flux also suppresses UPR ~(mt) induction in response to a block in mitochondrial fission, but not in response to the loss of spg-7 ~(AFG3L2), which encodes a mitochondrial metalloprotease. Finally, we found that blocking mitochondrial fusion or fission leads to increased levels of certain types of triacylglycerols and that this is at least partially reverted by the induction of autophagy. We propose that the breakdown of these triacylglycerols through autophagy leads to elevated metabolic activity, thereby increasing mitochondrial membrane potential and restoring mitochondrial and cellular homeostasis.
机译：妥协的线粒体融合或裂变破坏了细胞稳态;然而，潜在机制尚未完全理解。丧失c。 Elegans FZO-1〜（MFN）导致线粒体碎片，线粒体膜电位降低和线粒体展开蛋白反应的诱导（UPR〜（MT））。我们对基因进行了基因组RNAi筛网，即击倒抑制FZO-1〜（MFN）（LF）诱导UPR〜（MT）。在鉴定的299个基因中，143个编码自噬的负调节剂，其中许多以前没有涉及这种细胞质量控制机制。我们提出了通过增加线粒体膜电位而不是恢复线粒体形态来抑制增加的自噬透气抑制FZO-1〜（MFN）（LF）抑制UPR〜（MT）。此外，我们证明，增加的自噬磁体也抑制了对线粒体裂变中的嵌段的uPR〜（MT）诱导，但不响应SPG-7〜（AFG3L2）的损失，其编码线粒体金属蛋白酶。最后，我们发现阻断线粒体融合或裂变导致某些类型的三酰基甘油的水平增加，并且这至少部分地通过诱导自噬。我们提出通过自噬的这些三酰基甘油的击穿导致代谢活性升高，从而增加线粒体膜电位和恢复线粒体和细胞稳态。

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