Universität zu Köln

Tain, Luke S., Sehlke, Robert, Jain, Chirag, Chokkalingam, Manopriya, Nagaraj, Nagarjuna, Essers, Paul, Rassner, Mark, Groenke, Sebastian, Froelich, Jenny, Dieterich, Christoph, Mann, Matthias, Alic, Nazif ORCID: 0000-0003-0356-6600, Beyer, Andreas ORCID: 0000-0002-3891-2123 and Partridge, Linda ORCID: 0000-0001-9615-0094 (2017). A proteomic atlas of insulin signalling reveals tissue-specific mechanisms of longevity assurance. Mol. Syst. Biol., 13 (9). HOBOKEN: WILEY. ISSN 1744-4292

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Abstract

Lowered activity of the insulin/IGF signalling (IIS) network can ameliorate the effects of ageing in laboratory animals and, possibly, humans. Although transcriptome remodelling in long-lived IIS mutants has been extensively documented, the causal mechanisms contributing to extended lifespan, particularly in specific tissues, remain unclear. We have characterized the proteomes of four key insulin-sensitive tissues in a long-lived Drosophila IIS mutant and control, and detected 44% of the predicted proteome (6,085 proteins). Expression of ribosome-associated proteins in the fat body was reduced in the mutant, with a corresponding, tissue-specific reduction in translation. Expression of mitochondrial electron transport chain proteins in fat body was increased, leading to increased respiration, which was necessary for IIS-mediated lifespan extension, and alone sufficient to mediate it. Proteasomal subunits showed altered expression in IIS mutant gut, and gut-specific over-expression of the RPN6 proteasomal subunit, was sufficient to increase proteasomal activity and extend lifespan, whilst inhibition of proteasome activity abolished IIS-mediated longevity. Our study thus uncovered strikingly tissue-specific responses of cellular processes to lowered IIS acting in concert to ameliorate ageing.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tain, Luke S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sehlke, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Jain, Chirag UNSPECIFIED UNSPECIFIED UNSPECIFIED Chokkalingam, Manopriya UNSPECIFIED UNSPECIFIED UNSPECIFIED Nagaraj, Nagarjuna UNSPECIFIED UNSPECIFIED UNSPECIFIED Essers, Paul UNSPECIFIED UNSPECIFIED UNSPECIFIED Rassner, Mark UNSPECIFIED UNSPECIFIED UNSPECIFIED Groenke, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Froelich, Jenny UNSPECIFIED UNSPECIFIED UNSPECIFIED Dieterich, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Mann, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Alic, Nazif UNSPECIFIED orcid.org/0000-0003-0356-6600 UNSPECIFIED Beyer, Andreas UNSPECIFIED orcid.org/0000-0002-3891-2123 UNSPECIFIED Partridge, Linda UNSPECIFIED orcid.org/0000-0001-9615-0094 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-219358
DOI:	10.15252/msb.20177663
Journal or Publication Title:	Mol. Syst. Biol.
Volume:	13
Number:	9
Date:	2017
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1744-4292
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EXTENDS LIFE-SPAN; DROSOPHILA PGC-1 HOMOLOG; GENE-EXPRESSION; CAENORHABDITIS-ELEGANS; OXIDATIVE STRESS; MITOCHONDRIAL ACTIVITY; TRANSCRIPTION FACTOR; DIETARY RESTRICTION; METABOLIC PATHWAYS; MASS-SPECTROMETRY Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21935