Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Nakamura, Shuhei UNSPECIFIED orcid.org/0000-0002-1488-8317 UNSPECIFIED Karalay, Oezlem UNSPECIFIED UNSPECIFIED UNSPECIFIED Jaeger, Philipp S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Horikawa, Makoto UNSPECIFIED orcid.org/0000-0002-5094-7070 UNSPECIFIED Klein, Corinna UNSPECIFIED UNSPECIFIED UNSPECIFIED Nakamura, Kayo UNSPECIFIED UNSPECIFIED UNSPECIFIED Latza, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Templer, Sven E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dieterich, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Antebi, Adam UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language LIFE-SPAN EXTENSION; RESTRICTION-INDUCED LONGEVITY; TRANSFER-RNA SYNTHETASE; C-ELEGANS; CAENORHABDITIS-ELEGANS; TRANSCRIPTION FACTORS; LYSOSOMAL BIOGENESIS; LIPID-METABOLISM; AUTOPHAGY; PATHWAY Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28305