Nakamura, Shuhei ORCID: 0000-0002-1488-8317, Karalay, Oezlem, Jaeger, Philipp S., Horikawa, Makoto
ORCID: 0000-0002-5094-7070, Klein, Corinna, Nakamura, Kayo, Latza, Christian, Templer, Sven E., Dieterich, Christoph and Antebi, Adam
(2016).
Mondo complexes regulate TFEB via TOR inhibition to promote longevity in response to gonadal signals.
Nat. Commun., 7.
LONDON:
NATURE PUBLISHING GROUP.
ISSN 2041-1723
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.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-283053 | ||||||||||||||||||||||||||||||||||||||||||||
DOI: | 10.1038/ncomms10944 | ||||||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Nat. Commun. | ||||||||||||||||||||||||||||||||||||||||||||
Volume: | 7 | ||||||||||||||||||||||||||||||||||||||||||||
Date: | 2016 | ||||||||||||||||||||||||||||||||||||||||||||
Publisher: | NATURE PUBLISHING GROUP | ||||||||||||||||||||||||||||||||||||||||||||
Place of Publication: | LONDON | ||||||||||||||||||||||||||||||||||||||||||||
ISSN: | 2041-1723 | ||||||||||||||||||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||||||
Uncontrolled Keywords: |
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Refereed: | Yes | ||||||||||||||||||||||||||||||||||||||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/28305 |
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