Mitochondrial-derived compartments facilitate cellular adaptation to amino acid stress.
Mitochondrial-derived compartments facilitate cellular adaptation to amino acid stress.
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DOI：
10.1016/j.molcel.2021.08.021
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发表时间：
2021-09-16
期刊：
影响因子：
16
通讯作者：
Hughes AL
中科院分区：
文献类型：
--
作者：
Schuler MH;English AM;Xiao T;Campbell TJ;Shaw JM;Hughes AL
氨基酸是生命的基本组成部分。然而，越来越多的证据表明，升高的氨基酸引起与许多代谢紊乱相关的细胞毒性。细胞如何科普升高的氨基酸仍然知之甚少。在这里，我们表明，以前确定的细胞结构，衍生的隔室（MDC），功能，以保护细胞免受氨基酸应激。响应于氨基酸升高，MDC从线粒体产生，在线粒体中它们选择性地从细胞器中隔离和消耗SLC25A营养载体及其相关的输入受体Tom70。MDCs的产生促进氨基酸催化剂，并且它们的形成与通过多囊泡体（MVB）途径在质膜上去除转运蛋白同时发生。空泡氨基酸储存、MVB和MDC的组合损失使细胞对高氨基酸应激敏感。因此，我们建议，MDCs作为一个协调的细胞网络的一部分，通过翻译后营养转运蛋白重塑，促进氨基酸体内平衡。线粒体衍生的区室（MDC）是在经历溶酶体功能障碍的老化酵母细胞中观察到的神秘的线粒体亚结构域。舒勒等人现在表明，MDC是响应于细胞氨基酸的急性升高而产生的，并且这些结构域促进了细胞对氨基酸过量的适应。
Amino acids are essential building blocks of life. However, increasing evidence suggests that elevated amino acids cause cellular toxicity associated with numerous metabolic disorders. How cells cope with elevated amino acids remains poorly understood. Here, we show that a previously identified cellular structure, the mitochondrial-derived compartment (MDC), functions to protect cells from amino acid stress. In response to amino acid elevation, MDCs are generated from mitochondria, where they selectively sequester and deplete SLC25A nutrient carriers and their associated import receptor Tom70 from the organelle. Generation of MDCs promotes amino acid catabolism, and their formation occurs simultaneously with transporter removal at the plasma membrane via the multi-vesicular body (MVB) pathway. Combined loss of vacuolar amino acid storage, MVBs and MDCs renders cells sensitive to high amino acid stress. Thus, we propose that MDCs operate as part of a coordinated cell network that facilitates amino acid homoeostasis through post-translational nutrient transporter remodeling. Mitochondrial-derived compartments (MDCs) are enigmatic mitochondrial subdomains that have been observed in aged yeast cells experiencing lysosome dysfunction. Schuler et al. now show that MDCs are generated in response to acute elevation in cellular amino acids and that these domains facilitate cellular adaptation to amino acid overabundance.
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