4.7 Article

HLH-30-dependent rewiring of metabolism during starvation in C. elegans

期刊

AGING CELL
卷 20, 期 4, 页码 -

出版社

WILEY
DOI: 10.1111/acel.13342

关键词

aging; Caenorhabditis elegans; lipidomics; metabolomics; mitochondria; peroxisome; starvation; β ‐ oxidation

资金

  1. Danish Council for Independent Research, Natural Sciences [6108-00268A]

向作者/读者索取更多资源

The study demonstrates that starvation alters the abundance of hundreds of metabolites and lipid species in a temporal- and HLH-30-dependent manner, and that animals lacking the transcription factor HLH-30 rewires their metabolism to largely depend on functional peroxisomes during starvation. Furthermore, supplementation of exogenous fatty acids can prevent premature death of HLH-30 animals under starvation.
One of the most fundamental challenges for all living organisms is to sense and respond to alternating nutritional conditions in order to adapt their metabolism and physiology to promote survival and achieve balanced growth. Here, we applied metabolomics and lipidomics to examine temporal regulation of metabolism during starvation in wild-type Caenorhabditis elegans and in animals lacking the transcription factor HLH-30. Our findings show for the first time that starvation alters the abundance of hundreds of metabolites and lipid species in a temporal- and HLH-30-dependent manner. We demonstrate that premature death of hlh-30 animals under starvation can be prevented by supplementation of exogenous fatty acids, and that HLH-30 is required for complete oxidation of long-chain fatty acids. We further show that RNAi-mediated knockdown of the gene encoding carnitine palmitoyl transferase I (cpt-1) only impairs survival of wild-type animals and not of hlh-30 animals. Strikingly, we also find that compromised generation of peroxisomes by prx-5 knockdown renders hlh-30 animals hypersensitive to starvation, which cannot be rescued by supplementation of exogenous fatty acids. Collectively, our observations show that mitochondrial functions are compromised in hlh-30 animals and that hlh-30 animals rewire their metabolism to largely depend on functional peroxisomes during starvation, underlining the importance of metabolic plasticity to maintain survival.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据