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Complex effects of pH on ROS from mitochondrial complex II driven complex I reverse electron transport challenge its role in tissue reperfusion injury
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.08.31.275438v1?rss=1
Authors: Milliken, A. S., Kulkarni, C., Brookes, P. S.
Abstract:
Generation of mitochondrial reactive oxygen species (ROS) is an important process in triggering cellular necrosis and tissue infarction during ischemia-reperfusion (IR) injury. Ischemia results in accumulation of the metabolite succinate. Rapid oxidation of this succinate by mitochondrial complex II (Cx-II) during reperfusion reduces the co-enzyme Q (Co-Q) pool, thereby driving electrons backward into complex-I (Cx-I), a process known as reverse electron transport (RET), which is thought to be a major source of ROS. During ischemia, enhanced glycolysis results in an acidic cellular pH at the onset of reperfusion. While the process of RET within Cx-I is known to be enhanced by a high mitochondrial trans-membrane {Delta}pH, the impact of pH itself on the integrated process of Cx-II to Cx-I RET has not been fully studied. Using isolated mitochondria under conditions which mimic the onset of reperfusion (i.e., high [ADP]). We show that mitochondrial respiration (state 2 and state 3) as well as isolated Cx-II activity are impaired at acidic pH, whereas the overall generation of ROS by Cx-II to Cx-I RET was insensitive to pH. Together these data indicate that the acceleration of Cx-I RET ROS by {Delta}pH appears to be cancelled out by the impact of pH on the source of electrons, i.e. Cx-II. Implications for the role of Cx-II to Cx-I RET derived ROS in IR injury are discussed.
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By Multimodal LLCLink to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.08.31.275438v1?rss=1
Authors: Milliken, A. S., Kulkarni, C., Brookes, P. S.
Abstract:
Generation of mitochondrial reactive oxygen species (ROS) is an important process in triggering cellular necrosis and tissue infarction during ischemia-reperfusion (IR) injury. Ischemia results in accumulation of the metabolite succinate. Rapid oxidation of this succinate by mitochondrial complex II (Cx-II) during reperfusion reduces the co-enzyme Q (Co-Q) pool, thereby driving electrons backward into complex-I (Cx-I), a process known as reverse electron transport (RET), which is thought to be a major source of ROS. During ischemia, enhanced glycolysis results in an acidic cellular pH at the onset of reperfusion. While the process of RET within Cx-I is known to be enhanced by a high mitochondrial trans-membrane {Delta}pH, the impact of pH itself on the integrated process of Cx-II to Cx-I RET has not been fully studied. Using isolated mitochondria under conditions which mimic the onset of reperfusion (i.e., high [ADP]). We show that mitochondrial respiration (state 2 and state 3) as well as isolated Cx-II activity are impaired at acidic pH, whereas the overall generation of ROS by Cx-II to Cx-I RET was insensitive to pH. Together these data indicate that the acceleration of Cx-I RET ROS by {Delta}pH appears to be cancelled out by the impact of pH on the source of electrons, i.e. Cx-II. Implications for the role of Cx-II to Cx-I RET derived ROS in IR injury are discussed.
Copy rights belong to original authors. Visit the link for more info