Fig. 4.

Mitochondrial oxidant production and cell signaling. Mitochondrial ROS generated during electron transport diffuse out of the organelle, affecting expression of several transcription factors, including HIF-1, NFκB, and NFAT. At high or chronic levels, ROS causes damage to the mtDNA and organelle proteins, which can initiate innate immune responses via damage associated molecular patterns (DAMPs) release (see text, Immune functions and cell signaling). Similarly, in response to oxidative stress, a mitochondrial derived peptide MOTS-c, translocates from the mitochondrion to the nucleus in an AMP-kinase (AMPK) dependent manner where it binds several genes, including those with antioxidant response element (ARE)-containing promoter regions, and interacts with associated transcription factors such as Nrf2 to protect the cell against oxidative damage.