Work

Regulation of the protein disulfide proteome by mitochondria in mammalian cells

Year: 2007

Type: article

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.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.0702027104

Authors: Yi Yang, Yanli Song, Joseph Loscalzo

Institutions: Brigham and Women's Hospital, Harvard University, East China University of Science and Technology, State Key Laboratory of Bioreactor Engineering

Language: English

Topic: Redox biology and oxidative stress

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Ministry of Education of the People's Republic of China, National Institutes of Health, National Heart, Lung, and Blood Institute