A respiratory chain controlled signal transduction cascade in the mitochondrial intermembrane space mediates hydrogen peroxide signaling

05.10.2015

Patterson HC, Gerbeth C, Thiru P, Voegtle NF, Knoll M, Shahsafaei A, Samocha KE, Huang CX, Harden MM, Song R, Chen C, Kao J, Shi J, Salmon W, Shaul YD, Stokes MP, Silva JC, Bell GW, MacArthur DG, Ruland J, Meisinger C, Lodish HF.

Proc Natl Acad Sci U S A. 2015;112(42):E5679-88.

Proc Natl Acad Sci U S A.           online article

Both the mitochondrial respiratory chain and reactive oxygen species (ROS) control numerous physiological and pathological cellular responses. ROS such as hydrogen peroxide (H2O2) are thought to initiate signaling by broadly and nonspecifically redoxmodifying signaling molecules, suggesting that H2O2 signalingmay be distinct from other signal transduction pathways. Here, we provide evidence suggesting that H2O2 signaling is under control of what appears to be a typical signal transduction cascade that connects the respiratory chain to the mitochondrial intermembrane space-localized conserved Syk pathway and results in a focused signaling response in diverse cell types. The results thus reveal a mechanism that allows the respiratory chain to communicate with the remainder of the cell in response to ROS.