Reference - Detail
| RRC ID | 53480 |
|---|---|
| Author | Nakamura S, Karalay Ö, Jäger PS, Horikawa M, Klein C, Nakamura K, Latza C, Templer SE, Dieterich C, Antebi A. |
| Title | Mondo complexes regulate TFEB via TOR inhibition to promote longevity in response to gonadal signals. |
| Journal | Nat Commun |
| Abstract |
Germline removal provokes longevity in several species and shifts resources towards survival and repair. Several Caenorhabditis elegans transcription factors regulate longevity arising from germline removal; yet, how they work together is unknown. Here we identify a Myc-like HLH transcription factor network comprised of Mondo/Max-like complex (MML-1/MXL-2) to be required for longevity induced by germline removal, as well as by reduced TOR, insulin/IGF signalling and mitochondrial function. Germline removal increases MML-1 nuclear accumulation and activity. Surprisingly, MML-1 regulates nuclear localization and activity of HLH-30/TFEB, a convergent regulator of autophagy, lysosome biogenesis and longevity, by downregulating TOR signalling via LARS-1/leucyl-transfer RNA synthase. HLH-30 also upregulates MML-1 upon germline removal. Mammalian MondoA/B and TFEB show similar mutual regulation. MML-1/MXL-2 and HLH-30 transcriptomes show both shared and preferential outputs including MDL-1/MAD-like HLH factor required for longevity. These studies reveal how an extensive interdependent HLH transcription factor network distributes responsibility and mutually enforces states geared towards reproduction or survival. |
| Volume | 7 |
| Pages | 10944 |
| Published | 2016-3-22 |
| DOI | 10.1038/ncomms10944 |
| PII | ncomms10944 |
| PMID | 27001890 |
| PMC | PMC4804169 |
| MeSH | Animals Autophagy Basic Helix-Loop-Helix Transcription Factors / metabolism* Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism* Cell Nucleus / metabolism Gene Expression Profiling Gene Expression Regulation Gene Knockdown Techniques Germ Cells / metabolism Gonads / metabolism* Longevity* Phosphotransferases (Alcohol Group Acceptor) / metabolism* Protein Transport Reproduction Signal Transduction* Trans-Activators / metabolism* |
| IF | 12.121 |
| Times Cited | 24 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 21 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm1516 tm1978 tm311 tm1530 tm420 |