Functional role of mitochondrial reactive oxygen species in physiology

Abstract

Emails: p. stroh@ucl.ac.uk or a.abramov@ucl.ac.uk ABSTRACT The major energy generator in the cell -mitochondria produce reactive oxygen species as a by-product of a number of enzymatic reactions and ATP production. Emerging evidence suggests that mitochondrial ROS regulate diverse physiological parameters and that dysregulated ROS signalling may contribute to a development of pathologies which leads to human diseases. ROS produced in mitochondrial enzymes are trigger for monoamine-induced calcium signal in astrocytes, playing important role in physiological and pathophysiological response to dopamine. Generation of ROS in mitochondria leads to peroxidation of lipids, which is considered to be one of the most important mechanisms of cell injury under condition of oxidative stress. However, it also can induce activation of mitochondrial and cellular phospholipases that can trigger variety of the signals -from activation of ion channels to stimulation of calcium signal. Mitochondria are shown to be the oxygen sensor in astrocytes, therefore inhibition of respiration by hypoxia induces ROS production which leads to lipid peroxidation, activation of phospholipase C and induction of IP3-mediated calcium signal. Propagation of astrocytic calcium signal stimulates breathing activity in response to hypoxia. Thus, ROS produced in mitochondrial enzymes or electron transport chain can be used as a trigger for signalling cascades in central nervous system and deregulation of this process leads to pathology.

YAP Inhibits the Apoptosis and Migration of Human Rectal Cancer Cells via Suppression of JNK-Drp1-Mitochondrial Fission-HtrA2/Omi Pathways

“…5A-E, loss of Yap increased the levels of caspase 9 and caspase 3, suggesting that Yap inhibited mitochondrial apoptosis. Furthermore, pro-apoptotic factors (such as cyt-c and HtrA2/Omi) were released by mitochondria into the cytoplasm, where they activate caspase 9 and trigger subsequent caspase 3 activation [43]. Notably, the majority of studies to date have focused on cyt-c, with scant attention focused on HtrA2/Omi.…”

Mitochondria and aging: A role for the mitochondrial transition pore?

“…Reactive oxygen species were initially considered to be toxic molecules but a growing body of evidence suggests that oxidative stress, which is the result of a balance between the formation of ROS and their scavenging by antioxidant defenses, is regulated and participates to the maintenance of redox homeostasis and various cellular signaling pathways. In normal cells, the cellular and mitochondrial levels of ROS are safe and participate to the vital activity of the cell (Angelova & Abramov, 2016; Bae, Oh, Rhee, & Yoo, 2011; Dröge, 2002; Nickel, Kohlhaas, & Maack, 2014). However, under acute and chronic cellular stress conditions (e.g., acute ischemia and neurodegenerative diseases, respectively), the production of ROS is no longer regulated and becomes detrimental for the cell.…”

“…They are present in all cells of humans and animals (except red blood cells). They generate cellular energy, produce reactive oxygen species (ROS) that regulate physiological processes (Angelova & Abramov, 2016), and are involved in the control of cell death (Galluzzi, Kepp, Trojel‐Hansen, & Kroemer, 2012). Therefore, it is not surprising that mitochondria could be involved in the normal mammalian aging process.…”

Introduction to Special Issue on Mitochondrial Redox Signaling in Health and Disease

“…H2O2-mediated redox regulation of signaling and transcription entails thiol/disulfide exchange reactions [14,15]. In this special issue, mitochondrion-derived H2O2: (a) establishes a link between energy metabolism and inflammatory responses [16], acting on redox-sensitive targets such as Nrf2, NFB, JNK, IIS [17,18], and stimulates mitochondrial biogenesis [19]; (b) is at the interface between bioenergetics, autophagy, and circadian control [20]; (c) is controlled during cholesterol oxidation in steroidogenic cells and brings together the coordinated activities of peroxiredoxin III -the major H2O2 reducing system within mitochondria-sulfiredoxin, which recovers hyperoxidized peroxiredoxin III [21]; (d) is involved in the activation of phospholipases and is an important physiological function associated with O2 sensing in astrocytes and regulation of breathing [22]; (e) regulates mitogenic cellular signaling in proliferating cells through HIF activation and transcriptional activation of genes required for metabolic adaptations to proliferation and induction of angiogenesis [23]. It has been proposed that transducing an H2O2 signal can be accomplished by peroxiredoxin-2 and STAT3 [24].…”