FNDC-1-mediated mitophagy and ATFS-1 coordinate to protect against hypoxia-reoxygenation
FNDC-1-mediated mitophagy and ATFS-1 coordinate to protect against hypoxia-reoxygenation
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DOI：
10.1080/15548627.2021.1872885
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发表时间：
2021-01-21
期刊：
影响因子：
13.3
通讯作者：
Nehrke, Keith
中科院分区：
文献类型：
--
作者：
Lim, Yunki;Berry, Brandon;Nehrke, Keith
线粒体质量控制(MQC)平衡细胞器的适应和消除，潜在分子过程之间的机械性串扰影响随后的应激结果。Fundc1(FUN14结构域包含1)是哺乳动物对低氧复氧(HR)应激做出反应的一种有丝分裂受体。在这里，我们提供的证据表明，FNDC-1是FundC1的线虫直系同源物，它的丢失在HR的蠕虫模型中保护免受伤害。这种保护依赖于ATFS-1，一种对线粒体未折叠蛋白反应(UPRmt)至关重要的转录因子。全球信使核糖核酸和代谢物分析表明，fndc-1缺失后，依赖ATFS-1的应激反应和代谢重塑发生。这些数据支持FNDC-1在非缺氧性MQC中的作用，并进一步表明这些变化与随后的HR有关是预防性的。我们的结果强调了线粒体适应和消除之间的功能协调，线粒体适应和消除组织应激反应和新陈代谢重排，以保护免受HR损伤。
Mitochondrial quality control (MQC) balances organelle adaptation and elimination, and mechanistic crosstalk between the underlying molecular processes affects subsequent stress outcomes. FUNDC1 (FUN14 domain containing 1) is a mammalian mitophagy receptor that responds to hypoxia-reoxygenation (HR) stress. Here, we provide evidence that FNDC-1 is the C. elegans ortholog of FUNDC1, and that its loss protects against injury in a worm model of HR. This protection depends upon ATFS-1, a transcription factor that is central to the mitochondrial unfolded protein response (UPRmt). Global mRNA and metabolite profiling suggest that atfs-1-dependent stress responses and metabolic remodeling occur in response to the loss of fndc-1. These data support a role for FNDC-1 in non-hypoxic MQC, and further suggest that these changes are prophylactic in relation to subsequent HR. Our results highlight functional coordination between mitochondrial adaptation and elimination that organizes stress responses and metabolic rewiring to protect against HR injury.