Mondo complexes regulate TFEB via TOR inhibition to promote longevity in 
response to gonadal signals

Nakamura, S.; Karalay, O.; Jäger, P. S.; Horikawa, M.; Klein, C.; Nakamura, K.; Latza, C.; Templer , S. E.; Dieterich, C.; Antebi, A.

doi:10.1038/ncomms10944

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Mondo complexes regulate TFEB via TOR inhibition to promote longevity in response to gonadal signals

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Nakamura, S.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons130930

Karalay, O.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons282981

Jäger, P. S.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons282983

Horikawa, M.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons129636

Klein, C.
Dieterich – Computational RNA Biology and Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons129374

Nakamura, K.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons130926

Latza, C.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons129352

Dieterich, C.
Dieterich – Computational RNA Biology and Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons50070

Antebi, A.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

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http://www.ncbi.nlm.nih.gov/pubmed/27001890
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Citation

Nakamura, S., Karalay, O., Jäger, P. S., Horikawa, M., Klein, C., Nakamura, K., et al. (2016). Mondo complexes regulate TFEB via TOR inhibition to promote longevity in response to gonadal signals. Nat Commun, 7, 10944. doi:10.1038/ncomms10944.

Cite as: https://hdl.handle.net/21.11116/0000-000B-71A3-D

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.