Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers

Abstract

There are multiple sources of reactive oxygen species (ROS) in the cell. As a major site of ROS production, mitochondria have drawn considerable interest because it was recently discovered that mitochondrial ROS (mtROS) directly stimulate the production of proinflammatory cytokines and pathological conditions as diverse as malignancies, autoimmune diseases, and cardiovascular diseases all share common phenotype of increased mtROS production above basal levels. Several excellent reviews on this topic have been published, but ever-changing new discoveries mandated a more up-to-date and comprehensive review on this topic. Therefore, we update recent understanding of how mitochondria generate and regulate the production of mtROS and the function of mtROS both in physiological and pathological conditions. In addition, we describe newly developed methods to probe or scavenge mtROS and compare these methods in detail. Thorough understanding of this topic and the application of mtROS-targeting drugs in the research is significant towards development of better therapies to combat inflammatory diseases and inflammatory malignancies.

Induction of mitophagy-mediated antitumor activity with folate-appended methyl-β-cyclodextrin

“…Of the five ETC complexes in mitochondria, the ETC complex V plays an important role in ATP synthesis using proton-motive force. 39 In our study, FA-M-β-CyD elevated membrane potential in isolated mitochondria and lowered ATP production ( Figures 2B and 3A). Therefore, it is possible that FA-M-β-CyD may interfere with the function of ETC complex V in the mitochondria of KB cells (FR-α (+)).…”

Mitochondrial CaMKII inhibition in airway epithelium protects against allergic asthma

“…We next investigated potential mechanisms by which Mt-CaMKII inhibition protected against key features of allergic asthma. The proinflammatory transcription factor, NF-κB, is a master regulator of inflammation in allergic asthma (26)(27)(28)(29)(30). We therefore asked if Mt-CaMKII inhibition reduces NF-κB activity and/or expression.…”

Neutralization of Mitochondrial Superoxide by Superoxide Dismutase 2 Promotes Bacterial Clearance and Regulates Phagocyte Numbers in Zebrafish

“…While mitochondria can promote inflammation via NF-B signaling and NLRP3 inflammasome formation, inflammation can lead to mitochondrial dysfunction, which can compound the severity of exaggerated inflammatory conditions such as sepsis (4)(5)(6)(7)(8)(9)(10). As the site of the electron transport chain within cells, mitochondria are a major source of reactive oxygen species (ROS) (mainly superoxide anions).…”