Page 2 - G. Cell differentiation. division. and death

[G. Cell differentiation, division, and death-4]

Role of mitochondrial reactive oxygen species in TNF-α-

induced necroptosis

Jiyoung Lee¹, Sang Won Kang¹˙*

¹Department of Life Science, Ewha Womans University, seoul 03760, south korea

Cell death is indispensable for maintaining homeostasis in organism. Because unregulated cell death causes various
diseases such as cancer and autoimmune diseases, it is important to study the mechanisms to control cell death.
Reactive oxygen species (ROS) are robustly produced during the cell death. There are three types of ROS, such as

superoxide anion (O2˙ˉ), hydrogen peroxide (H2O2), and hydroxyl radical (OH). However, few studies have identified

types of ROS in different cell death pathways. Since we have shown that the 2-Cys peroxiredoxin (Prx) isoforms, Prx
I and Prx II, regulate different apoptosis pathways via H2O2, a question was raised whether mitochondrial ROS is
involved in the necroptosis. In this study, we show that different types of ROS are produced in the TNFα-induced

apoptosis and necroptosis. Specifically, the TNFα-induced necroptosis accompanies with mitochondrial superoxide
anion. Moreover, the mitochondria superoxide anion was regulated by a necroptosis kinase RIPK3. Importantly,

blocking mitochondrial superoxide production did not affect the necroptosis. Thus, the study implicates a selectivity
on ROS production depending on cell death programs.