Universität zu Köln

Ravanelli, Sonia ORCID: 0000-0002-8511-9339, Li, Qiaochu ORCID: 0000-0001-8032-9110, Annibal, Andrea ORCID: 0000-0003-4311-5417, Trifunovic, Aleksandra ORCID: 0000-0002-5472-3517, Antebi, Adam and Hoppe, Thorsten (2022). Reprograming of proteasomal degradation by branched chain amino acid metabolism. Aging Cell, 21 (12). HOBOKEN: WILEY. ISSN 1474-9726

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Abstract

Branched-chain amino acid (BCAA) metabolism is a central hub for energy production and regulation of numerous physiological processes. Controversially, both increased and decreased levels of BCAAs are associated with longevity. Using genetics and multi-omics analyses in Caenorhabditis elegans, we identified adaptive regulation of the ubiquitin-proteasome system (UPS) in response to defective BCAA catabolic reactions after the initial transamination step. Worms with impaired BCAA metabolism show a slower turnover of a GFP-based proteasome substrate, which is suppressed by loss-of-function of the first BCAA catabolic enzyme, the branched-chain aminotransferase BCAT-1. The exogenous supply of BCAA-derived carboxylic acids, which are known to accumulate in the body fluid of patients with BCAA metabolic disorders, is sufficient to regulate the UPS. The link between BCAA intermediates and UPS function presented here sheds light on the unexplained role of BCAAs in the aging process and opens future possibilities for therapeutic interventions.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ravanelli, Sonia UNSPECIFIED orcid.org/0000-0002-8511-9339 UNSPECIFIED Li, Qiaochu UNSPECIFIED orcid.org/0000-0001-8032-9110 UNSPECIFIED Annibal, Andrea UNSPECIFIED orcid.org/0000-0003-4311-5417 UNSPECIFIED Trifunovic, Aleksandra UNSPECIFIED orcid.org/0000-0002-5472-3517 UNSPECIFIED Antebi, Adam UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoppe, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-666416
DOI:	10.1111/acel.13725
Journal or Publication Title:	Aging Cell
Volume:	21
Number:	12
Date:	2022
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1474-9726
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MITOCHONDRIAL BIOGENESIS; PROTEIN HOMEOSTASIS; 26S PROTEASOME; LIFE-SPAN; HEALTH Multiple languages Cell Biology; Geriatrics & Gerontology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66641