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

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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
Creators:
CreatorsEmailORCIDORCID Put Code
Nakamura, ShuheiUNSPECIFIEDorcid.org/0000-0002-1488-8317UNSPECIFIED
Karalay, OezlemUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jaeger, Philipp S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Horikawa, MakotoUNSPECIFIEDorcid.org/0000-0002-5094-7070UNSPECIFIED
Klein, CorinnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nakamura, KayoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Latza, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Templer, Sven E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dieterich, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Antebi, AdamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
LIFE-SPAN EXTENSION; RESTRICTION-INDUCED LONGEVITY; TRANSFER-RNA SYNTHETASE; C-ELEGANS; CAENORHABDITIS-ELEGANS; TRANSCRIPTION FACTORS; LYSOSOMAL BIOGENESIS; LIPID-METABOLISM; AUTOPHAGY; PATHWAYMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/28305

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