Cancer is a leading cause of death worldwide. In many cases, the treatment of the disease is limited due to the metastasis of cells to distant locations of the body through the blood and lymphatic drainage. Most of the anticancer therapeutic options focus mainly on the inhibition of tumor cell growth or the induction of cell death, and do not consider the molecular basis of metastasis. The aim of this work is to provide a comprehensive review focusing on cancer metastasis and the mitogen-activated protein kinase (MAPK) pathway (ERK/JNK/P38 signaling) as a crucial modulator of this process.
Sixteen adult, 4-month-old male Wistar rats were randomly assigned to the training group (n = 8) or the control group (n = 8). We elucidated the effects of 8 weeks of endurance training on coenzyme Q (Q) content and the formation of reactive oxygen species (ROS) at the tissue level and in isolated mitochondria of the rat heart, liver and brain. We demonstrated that endurance training enhanced mitochondrial biogenesis in all tested organs, while a significant increase in the Q redox state was observed in the heart and brain, indicating an elevated level of QH2 as an antioxidant. Moreover, endurance training increased the mQH2 antioxidant pool in the mitochondria of the heart and liver, but not in the brain. At the tissue and isolated mitochondria level, an increase in ROS formation was only observed in the heart. ROS formation observed in the mitochondria of individual rat tissues after training may be associated with changes in the activity/amount of individual components of the oxidative phosphorylation system and its molecular organization, as well as with the size of the oxidized pool of mitochondrial Q acting as an electron carrier in the respiratory chain. Our results indicate that tissue-dependent changes induced by endurance training in the cellular and mitochondrial QH2 pool acting as an antioxidant and in the mitochondrial Q pool serving the respiratory chain may serve important roles in energy metabolism, redox homeostasis and the level of oxidative stress.
Mitochondrial coenzyme Q (mtQ) of the inner mitochondrial membrane is a redox active mobile carrier in the respiratory chain that transfers electrons between reducing dehydrogenases and oxidizing pathway(s). mtQ is also involved in mitochondrial reactive oxygen species (mtROS) formation through the mitochondrial respiratory chain. Some mtQ-binding sites related to the respiratory chain can directly form the superoxide anion from semiubiquinone radicals. On the other hand, reduced mtQ (ubiquinol, mtQH2) recycles other antioxidants and directly acts on free radicals, preventing oxidative modifications. The redox state of the mtQ pool is a central bioenergetic patameter that alters in response to changes in mitochondrial function. It reflects mitochondrial bioenergetic activity and mtROS formation level, and thus the oxidative stress associated with the mitochondria. Surprisingly, there are few studies describing a direct relationship between the mtQ redox state and mtROS production under physiological and pathological conditions. Here, we provide a first overview of what is known about the factors affecting mtQ redox homeostasis and its relationship to mtROS production. We have proposed that the level of reduction (the endogenous redox state) of mtQ may be a useful indirect marker to assess total mtROS formation. A higher mtQ reduction level (mtQH2/mtQ total ) indicates greater mtROS formation. The mtQ reduction level, and thus the mtROS formation, depends on the size of the mtQ pool and the activity of the mtQ-reducing and mtQH2-oxidizing pathway(s) of respiratory chain. We focus on a number of physiological and pathophysiological factors affecting the amount of mtQ and thus its redox homeostasis and mtROS production level.
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