Mitochondrial ROS Signaling in Organismal Homeostasis

Abstract

Summary Generation, transformation, and utilization of organic molecules in support of cellular differentiation, growth, and maintenance are basic tenets that define life. In eukaryotes, mitochondrial oxygen consumption plays a central role in these processes. During the process of oxidative phosphorylation, mitochondria utilize oxygen to generate ATP from organic fuel molecules but in the process also produce reactive oxygen species (ROS). While ROS have long been appreciated for their damage-promoting, detrimental effects, there is now a greater understanding of their roles as signaling molecules. Here, we review mitochondrial ROS-mediated signaling pathways with an emphasis on how they are involved in various basal and adaptive physiological responses that control organismal homeostasis.

Prdm16 is crucial for progression of the multipolar phase during neural differentiation of the developing neocortex

“…During oxidative phosphorylation, mitochondria use oxygen to generate ATP from organic fuel molecules, but in the process they also produce intracellular reactive oxygen species (ROS) (Shadel and Horvath, 2015). Although ROS have long been known for their damage-promoting detrimental effects, their roles as signaling molecules are now becoming better understood (Shadel and Horvath, 2015).…”

Mitochondrial dynamics in neuronal injury, development and plasticity

“…Precipitous mitochondrial fission or fragmentation has been observed to accompany ROS production and oxidative damage in response to a variety of neuronal insults (Yu et al, 2006;Cho et al, 2012;Ebenezer et al, 2010;Gan et al, 2014;Grohm et al, 2010). However, mitochondria-derived ROS have also been shown to act as a homeostatic signaling molecule in various physiological processes, including synaptic transmission (Shadel and Horvath, 2015;Hamanaka and Chandel, 2010). During synaptic transmission, the mitochondrial ATP generation produces ROS, which can regulate the strength of synaptic transmission.…”

“…However, this is an oversimplification of mitochondrial physiology. In addition to carrying out ATP synthesis through oxidative phosphorylation, mitochondria are also important for Ca 2+ signaling (Brini et al, 2014;Nicholls, 2005;Duchen, 2000;Clapham, 2007), cell death (Tait and Green, 2013;Duchen, 2000), steroid synthesis (Miller, 2011), reactive oxygen species (ROS) production and sequestration (Zorov et al, 2014;Hamanaka and Chandel, 2010;Shadel and Horvath, 2015;Accardi et al, 2014), and neurotransmitter synthesis and inactivation (Rowley et al, 2012;Bak et al, 2005;Waagepetersen et al, 2000). Given the importance of processes, such as ATP production, Ca 2+ transients, neurotransmitter metabolism and ROS signaling, in synaptic transmission it is not surprising that recent work has illustrated that perturbations in mitochondrial physiology exert profound effects on neuronal development and function.…”

Acetylcholinesterase-independent protective effects of huperzine A against iron overload-induced oxidative damage and aberrant iron metabolism signaling in rat cortical neurons

“…ROS cause mitochondrial dysfunction because mitochondria are extremely sensitive to oxidative stress [56] . Moreover, mitochondria also produce ROS during the process of ATP generation [57] , thus suggesting that the effects of HupA on ROS decreases and mitochondrial protection may act synergistically. Therefore, the obvious ROSdecreasing effect of HupA might also have positively contributed to its beneficial effects on mitochondrial function in the FAC-exposed cortical neurons.…”