University of Oulu

Daniela Mennerich, Sakari Kellokumpu, and Thomas Kietzmann. Antioxidants & Redox Signaling. Jan 2019. 113-137.

Hypoxia and reactive oxygen species as modulators of endoplasmic reticulum and Golgi homeostasis

Saved in:
Author: Mennerich, Daniela1; Kellokumpu, Sakari1; Kietzmann, Thomas1
Organizations: 1Faculty of Biochemistry and Molecular Medicine, and Biocenter Oulu, University of Oulu, FI-90014 Oulu, Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 0.3 MB)
Persistent link:
Language: English
Published: Mary Ann Liebert, 2019
Publish Date: 2021-03-03


Significance: Eukaryotic cells execute various functions in subcellular compartments or organelles for which cellular redox homeostasis is of importance. Apart from mitochondria, hypoxia and stress-mediated formation of reactive oxygen species (ROS) were shown to modulate endoplasmic reticulum (ER) and Golgi apparatus (GA) functions.

Recent Advances: Research during the last decade has improved our understanding of disulfide bond formation, protein glycosylation and secretion, as well as pH and redox homeostasis in the ER and GA. Thus, oxygen (O₂) itself, NADPH oxidase (NOX) formed ROS, and pH changes appear to be of importance and indicate the intricate balance of intercompartmental communication.

Critical Issues: Although the interplay between hypoxia, ER stress, and Golgi function is evident, the existence of more than 20 protein disulfide isomerase family members and the relative mild phenotypes of, for example, endoplasmic reticulum oxidoreductin 1 (ERO1)- and NOX4-knockout mice clearly suggest the existence of redundant and alternative pathways, which remain largely elusive.

Future Directions: The identification of these pathways and the key players involved in intercompartmental communication needs suitable animal models, genome-wide association, as well as proteomic studies in humans. The results of those studies will be beneficial for the understanding of the etiology of diseases such as type 2 diabetes, Alzheimer’s disease, and cancer, which are associated with ROS, protein aggregation, and glycosylation defects.

see all

Series: Antioxidants & redox signaling
ISSN: 1523-0864
ISSN-E: 1557-7716
ISSN-L: 1523-0864
Volume: 30
Issue: 1
Pages: 113 - 117
DOI: 10.1089/ars.2018.7523
Type of Publication: A2 Review article in a scientific journal
Field of Science: 1182 Biochemistry, cell and molecular biology
1184 Genetics, developmental biology, physiology
217 Medical engineering
3111 Biomedicine
3122 Cancers
Funding: This work was supported by the Finnish Academy of Science to S.K., T.K., the Jane and Aatos Erkko Foundation to T.K. as well as by the Biocenter Oulu, and the University of Oulu.
Copyright information: © 2018, Mary Ann Liebert, Inc., publishers.