| 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
|
| Resource |
| C.elegans |
tm1516
tm1978
tm311
tm1530
tm420 |
