Reactive Oxygen Species and Mitochondrial Dynamics: The Yin and Yang of Mitochondrial Dysfunction and Cancer Progression

Abstract

Mitochondria are organelles with a highly dynamic ultrastructure maintained by a delicate equilibrium between its fission and fusion rates. Understanding the factors influencing this balance is important as perturbations to mitochondrial dynamics can result in pathological states. As a terminal site of nutrient oxidation for the cell, mitochondrial powerhouses harness energy in the form of ATP in a process driven by the electron transport chain. Contemporaneously, electrons translocated within the electron transport chain undergo spontaneous side reactions with oxygen, giving rise to superoxide and a variety of other downstream reactive oxygen species (ROS). Mitochondrially-derived ROS can mediate redox signaling or, in excess, cause cell injury and even cell death. Recent evidence suggests that mitochondrial ultrastructure is tightly coupled to ROS generation depending on the physiological status of the cell. Yet, the mechanism by which changes in mitochondrial shape modulate mitochondrial function and redox homeostasis is less clear. Aberrant mitochondrial morphology may lead to enhanced ROS formation, which, in turn, may deteriorate mitochondrial health and further exacerbate oxidative stress in a self-perpetuating vicious cycle. Here, we review the latest findings on the intricate relationship between mitochondrial dynamics and ROS production, focusing mainly on its role in malignant disease.

Toll‐like receptor 2 regulates metabolic reprogramming in gastric cancer via superoxide dismutase 2

“…Interestingly, further analysis of many key redox genes implicated in other antioxidant systems including SOD family members, the major H 2 O 2 scavenger catalase (CAT), glutathione peroxidase (GPX) family members, glutamate‐cysteine ligase catalytic subunit (GCLC), glutathione synthetase (GSS), NAPDH oxidase (NOXs) family members and dual oxidase1 (DUOX1), indicated that only SOD2 was uniquely upregulated in both high TLR2‐expressing GC cells we studied (Figs. e– g ).…”

Empagliflozin normalizes the size and number of mitochondria and prevents reduction in mitochondrial size after myocardial infarction in diabetic hearts

“…; Jezek et al. ). Generation of ROS in mitochondria in the diabetic heart is increased by multiple mechanisms (Bugger and Abel ), and OLETF at 25–30 weeks of age show mild diastolic dysfunction with preserved systolic function (Takada et al.…”

“…Interestingly, exposure of endothelial cells to a high concentration of glucose upregulated Fis1 expression and elevated mitochondrial levels of ROS (Shenouda et al 2011). On the other hand, endogenous ROS and exogenous ROS have been shown to induce shortening and fragmentation of mitochondria in cardiac and noncardiac cells (Huang et al 2016;Tsushima et al 2017;Jezek et al 2018). Generation of ROS in mitochondria in the diabetic heart is increased by multiple mechanisms (Bugger and Abel 2010), and OLETF at 25-30 weeks of age show mild diastolic dysfunction with preserved systolic function (Takada et al 2012;Kouzu et al 2015).…”

Nicotinamide mononucleotide alters mitochondrial dynamics by SIRT3‐dependent mechanism in male mice

“…Mitochondrial dynamics and ROS production are intrinsically linked. The fragmented mitochondrial phenotype is observed with mitochondrial ROS overproduction (Huang et al, 2016;Jezek, Cooper, & Strich, 2018). Recent studies have shown that blocking or inhibiting Drp1 in ROS-mediated oxidative stress improved mitochondrial function and decreased fragmentation (Gan, Huang, Yu, Yu, & Yan, 2015;Zhang et al, 2017).…”