Interplay between redox and protein homeostasis

Abstract

The subcellular compartments of eukaryotic cells are characterized by different redox environments. Whereas the cytosol, nucleus and mitochondria are more reducing, the endoplasmic reticulum represents a more oxidizing environment. As the redox level controls the formation of intra-and inter-molecular disulfide bonds, the folding of proteins is tightly linked to its environment. The proteostasis network of each compartment needs to be adapted to the compartmental redox properties. In addition to chaperones, also members of the thioredoxin superfamily can influence the folding of proteins by regulation of cysteine reduction/oxidation. This review will focus on thioredoxin superfamily members and chaperones of C. elegans, which play an important role at the interface between redox and protein homeostasis. Additionally, this review will highlight recent methodological developments on in vivo and in vitro assessment of the redox state and their application to provide insights into the high complexity of redox and proteostasis networks of C. elegans.

Comparative Proteomics Indicates That Redox Homeostasis Is Involved in High- and Low-Temperature Stress Tolerance in a Novel Wucai (Brassica campestris L.) Genotype

“…The accumulation of ROS depends on changes in the redox state of cells, and thus it could function to reset the redox state and maintain redox homeostasis [3]. Because the sulfur-containing amino acids cysteine and methionine are sensitive to redox potential, changes in the redox state can affect protein structure and folding [4]. Changes in redox potential may also alter enzyme activity, biochemical reactions, and plant physiological processes, which can negatively affect plant survival [5].…”

Reductive stress promotes protein aggregation and impairs neurogenesis

“…The subcellular compartments within a cell exhibit unique redox environments [ 34 ]. Of note, while mitochondria, cytosol, and the nucleus experience a reductive redox milieu, the endoplasmic reticulum (ER) holds a relatively oxidative redox state [ [35] , [36] , [37] ]. As we established a RS condition in sulforaphane-treated N2a cells, we postulated that this may disrupt the ER function.…”

Loss of glutathione redox homeostasis impairs proteostasis by inhibiting autophagy-dependent protein degradation

“…Organisms as distant as the nematode C. elegans and humans contain a similar number of cysteine residues in their proteome, estimated in about 210,000 10 . Importantly, their respective thioredoxin and glutathione redox systems are highly conserved 11 , supporting the use of C. elegans as a simple model relevant to addressing key questions in redox biology 12,13 . In worms, the thioredoxin system is dispensable for redox homeostasis as null or strong loss of function mutants of 5 the genes encoding the cytoplasmic and mitochondrial thioredoxins (trx-1, trx-2 and trx-3) and thioredoxin reductases (trxr-1 and trxr-2) are viable and superficially wild type 14,15,16,17 .…”