title: Regulation of the protein disulfide proteome by mitochondria in mammalian cells.
abstract: The majority of protein disulfides in cells is considered an important inert structural, rather than a dynamic regulatory, determinant of protein function. Here, we show that some disulfides in proteins also are regulated by cell redox status with functional consequences. We find that reactive oxygen species (ROS) produced by mitochondria are actively used by cells to facilitate cell-surface protein disulfide formation, as well as folding and transport, in mammalian cells. Inhibition of mitochondrial ROS production suppresses protein disulfide formation and induces reductive stress, leading to dysfunction and retention (possibly in the Golgi, in part) of a group of cell-surface disulfide-containing proteins. Sparsely cultured cells produce less ROS than confluent cells do, which leads to decreased disulfide formation and decreased activity of a subgroup of disulfide-containing cell-surface receptors. These data support the concept of two subproteomes comprising the disulfide proteome, a structural group and a redox-sensitive regulatory group, with the latter having direct functional consequences for the cell.
authors.affiliation: Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Yanli
authors.initials: Y
authors.lastname: Song
authors.forename: Joseph
authors.initials: J
authors.lastname: Loscalzo
mesh_terms: D000818:Animals; D002477:Cells / Q000378:metabolism*; D004220:Disulfides / Q000378:metabolism*; D008322:Mammals; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology; D008928:Mitochondria / Q000502:physiology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D020543:Proteome; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004220:Disulfides; D008565:Membrane Proteins; D020543:Proteome; D017382:Reactive Oxygen Species