Abstract:
: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.
journal_name
Redox Bioljournal_title
Redox biologyauthors
Sweeny EA,Schlanger S,Stuehr DJdoi
10.1016/j.redox.2020.101656subject
Has Abstractpub_date
2020-09-01 00:00:00pages
101656issn
2213-2317pii
S2213-2317(20)30861-2journal_volume
36pub_type
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