Dynamic regulation of NADPH oxidase 5 by intracellular heme levels and cellular chaperones. Redox Biol 2020 Sep;36:101656
Date
08/02/2020Pubmed ID
32738790Pubmed Central ID
PMC7394750DOI
10.1016/j.redox.2020.101656Scopus ID
2-s2.0-85088630674 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
NADPH oxidase 5 (NOX5) is a transmembrane signaling enzyme that produces superoxide in response to elevated cytosolic calcium. In addition to its association with numerous human diseases, NOX5 has recently been discovered to play crucial roles in the immune response and cardiovascular system. Details of NOX5 maturation, and specifically its response to changes in intracellular heme levels have remained unclear. Here we establish an experimental system in mammalian cells that allows us to probe the influence of heme availability on ROS production by NOX5. We identified a mode of dynamic regulatory control over NOX5 activity through modulation of its heme saturation and oligomeric state by intracellular heme levels and Hsp90 binding. This regulatory mechanism allows for fine-tuning and reversible modulation of NOX5 activity in response to stimuli.
Author List
Sweeny EA, Schlanger S, Stuehr DJAuthor
Elizabeth Sweeny PhD Assistant Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsHeme
Humans
Membrane Proteins
NADPH Oxidase 5
NADPH Oxidases
Reactive Oxygen Species
