Universität zu Köln

Hoppe, Thorsten ORCID: 0000-0002-4734-9352 and Cohen, Ehud (2020). Organismal Protein Homeostasis Mechanisms. Genetics, 215 (4). S. 889 - 902. BETHESDA: GENETICS SOCIETY AMERICA. ISSN 1943-2631

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Abstract

Sustaining a healthy proteome is a lifelong challenge for each individual cell of an organism. However, protein homeostasis or proteostasis is constantly jeopardized since damaged proteins accumulate under proteotoxic stress that originates from ever-changing metabolic, environmental, and pathological conditions. Proteostasis is achieved via a conserved network of quality control pathways that orchestrate the biogenesis of correctly folded proteins, prevent proteins from misfolding, and remove potentially harmful proteins by selective degradation. Nevertheless, the proteostasis network has a limited capacity and its collapse deteriorates cellular functionality and organismal viability, causing metabolic, oncological, or neurodegenerative disorders. While cell-autonomous quality control mechanisms have been described intensely, recent work onCaenorhabditis eleganshas demonstrated the systemic coordination of proteostasis between distinct tissues of an organism. These findings indicate the existence of intricately balanced proteostasis networks important for integration and maintenance of the organismal proteome, opening a new door to define novel therapeutic targets for protein aggregation diseases. Here, we provide an overview of individual protein quality control pathways and the systemic coordination between central proteostatic nodes. We further provide insights into the dynamic regulation of cellular and organismal proteostasis mechanisms that integrate environmental and metabolic changes. The use ofC. elegansas a model has pioneered our understanding of conserved quality control mechanisms important to safeguard the organismal proteome in health and disease.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hoppe, Thorsten UNSPECIFIED orcid.org/0000-0002-4734-9352 UNSPECIFIED Cohen, Ehud UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-324845
DOI:	10.1534/genetics.120.301283
Journal or Publication Title:	Genetics
Volume:	215
Number:	4
Page Range:	S. 889 - 902
Date:	2020
Publisher:	GENETICS SOCIETY AMERICA
Place of Publication:	BETHESDA
ISSN:	1943-2631
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HEAT-SHOCK RESPONSE; CAENORHABDITIS-ELEGANS; MOLECULAR CHAPERONES; ENDOPLASMIC-RETICULUM; C. ELEGANS; ELECTRON-TRANSPORT; STRESS RESISTANCE; MITOCHONDRIAL UPR; RNA INTERFERENCE; GAMMA-SECRETASE Multiple languages Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/32484