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Reprograming of Proteasomal Degradation by Branched Chain Amino Acid Metabolism

ABSTRACT: Branched chain amino acids (BCAAs) play an important role in energy and protein regulation. Defects in BCAA metabolism are linked to numerous pathologies, including diabetes, neurodegeneration, and premature aging. Isovaleric acidemia is a metabolic disease caused by defective leucine breakdown and an abnormal accumulation of isovaleric acid in the body fluids; however, the cytotoxic effects caused by excess isovaleric acid remained unclear. Here, we provide a regulatory connection between BCAA metabolism and the ubiquitin/proteasome-system (UPS) in Caenorhabditis elegans. Multi-omic analysis identified that worms lacking the isovaleryl-CoA dehydrogenase IVD-1 exhibit reduced expression of regulatory proteasome subunits and defects in ubiquitin-dependent proteolysis. Conversely, proteasomal protein degradation was supported by the branched chain amino transferase BCAT-1. Adding extra isovaleric acid to the growth medium triggered UPS defects, implying a causative role of perturbed proteostasis in isovaleric academia.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Caenorhabditis Elegans

TISSUE(S): Whole Body

SUBMITTER: Prerana Wagle

LAB HEAD: Thorsten Hoppe

PROVIDER: PXD028286 | Pride | 2022-09-22

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	1873-library.xlsx	Xlsx
	1873.sne	Other
	1873_Report_PG_no1.xlsx	Xlsx
	20190827_Q1_JK_ColID_869c_ProjID_1873_Hoppe_sample_01.raw	Raw
	20190827_Q1_JK_ColID_869c_ProjID_1873_Hoppe_sample_02.raw	Raw

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Reprograming of Proteasomal Degradation by Branched Chain Amino Acid Metabolism

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