論文 - 詳細
| RRC ID | 76328 |
|---|---|
| 著者 | Wong SQ, Ryan CJ, Bonal DM, Mills J, Lapierre LR. |
| タイトル | Neuronal HLH-30/TFEB modulates peripheral mitochondrial fragmentation to improve thermoresistance in Caenorhabditis elegans. |
| ジャーナル | Aging Cell |
| Abstract |
Transcription factor EB (TFEB) is a conserved master transcriptional activator of autophagy and lysosomal genes that modulates organismal lifespan regulation and stress resistance. As neurons can coordinate organism-wide processes, we investigated the role of neuronal TFEB in stress resistance and longevity. To this end, the Caenorhabditis elegans TFEB ortholog, hlh-30, was rescued panneuronally in hlh-30 loss of function mutants. While important in the long lifespan of daf-2 animals, neuronal HLH-30/TFEB was not sufficient to restore normal lifespan in short-lived hlh-30 mutants. However, neuronal HLH-30/TFEB rescue mediated robust improvements in the heat stress resistance of wildtype but not daf-2 animals. Notably, these mechanisms can be uncoupled, as neuronal HLH-30/TFEB requires DAF-16/FOXO to regulate longevity but not thermoresistance. Through further transcriptomics profiling and functional analysis, we discovered that neuronal HLH-30/TFEB modulates neurotransmission through the hitherto uncharacterized protein W06A11.1 by inducing peripheral mitochondrial fragmentation and organismal heat stress resistance in a non-cell autonomous manner. Taken together, this study uncovers a novel mechanism of heat stress protection mediated by neuronal HLH-30/TFEB. |
| 巻・号 | 22(3) |
| ページ | e13741 |
| 公開日 | 2023-3-1 |
| DOI | 10.1111/acel.13741 |
| PMID | 36419219 |
| PMC | PMC10014052 |
| MeSH | Animals Basic Helix-Loop-Helix Transcription Factors / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Forkhead Transcription Factors / metabolism Longevity / genetics Neurons / metabolism Transcription Factors / metabolism |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 9 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.2 |
| リソース情報 | |
| 線虫 | tm1978 tm4056 |