Proteotoxic stress and ageing triggers the loss of redox homeostasis across cellular compartments. (30th July 2015)

• Record Type: Journal Article
• Authors: Kirstein, Janine; Morito, Daisuke; Kakihana, Taichi; Sugihara, Munechika; Minnen, Anita; Hipp, Mark S; Nussbaum‐Krammer, Carmen; Kasturi, Prasad; Hartl, F Ulrich; Nagata, Kazuhiro; Morimoto, Richard I
• Is Part Of: EMBO journal. Volume 34:Number 18(2015)
• Page Start: 2334
• Page End: 2349
• Publication Date: 2015-07-30
• Subjects: Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.201591711
• Languages: English
• ISSNs: 0261-4189

Abstract

<abstract abstract-type="main" id="embj201591711-abs-0001"> <title>Abstract</title> <p>The cellular proteostasis network integrates the protein folding and clearance machineries in multiple sub‐cellular compartments of the eukaryotic cell. The endoplasmic reticulum (ER) is the site of synthesis and folding of membrane and secretory proteins. A distinctive feature of the ER is its tightly controlled redox homeostasis necessary for the formation of inter‐ and intra‐molecular disulphide bonds. Employing genetically encoded <italic>in vivo</italic> sensors reporting on the redox state in an organelle‐specific manner, we show in the nematode <italic>Caenorhabditis elegans</italic> that the redox state of the ER is subject to profound changes during worm lifetime. In young animals, the ER is oxidizing and this shifts towards reducing conditions during ageing, whereas in the cytosol the redox state becomes more oxidizing with age. Likewise, the redox state in the cytosol and the ER change in an opposing manner in response to proteotoxic challenges in <italic>C. elegans</italic> and in HeLa cells revealing conservation of redox homeostasis. Moreover, we show that organelle redox homeostasis is regulated across tissues within <italic>C. elegans</italic> providing a new measure for organismal fitness.</p> </abstract>