Saturday, April 09, 2016
Warming our bodies: the free radicals
All of a sudden, the reactive oxygen species (ROS; aka 'free radicals') are coming back to attention - not as the bad guys, as they are normally portrayed, but as important good guys involved and controlling useful cellular signalling.
A recent paper in Nature (Chouchani, Kazak et al - Nature, 532: 103 - here) shows evidence that the cold-induced thermogenesis in the BAT (brown adipose tissue), a process mediated by a well known protein - the uncoupling protein 1 (UCP1), which dissipates the proton gradient across the inner mitochondrial membrane, is, in fact, activated by ROS. The mitochondrial free radicals induce thiol oxidation (thiols always being quite sensitive to the redox potential), targeting in particular a cysteine moiety(Cys 253) in the UCP1 protein, and this oxidation is associated with the activation of the UCP1-dependent termogenic respiration.
(panel h from their fig. 4, describing the activation process; with the added information that the process is activated by adrenergic stimulation, something only briefly address in the paper).
As per usual with the current Nature papers, a lot of data is not presented in the print version, but available as an Extended Data add-on.
The import at and crucial piece of evidence is that when MitoQ is used (a novel, magic drug, used in human clinical trials, with a powerful antioxidant activity, localised specifically to the mitochondria - see this 2012 review (open access)), and thus when the ROS production in the mitochondria is reduced, the thermogenesis (and the associated oxygen-consumption) is reduced.
Certainly, there are a number of important questions that need answering starting with how does cold triggers the specific increase in ROS? One potential explanation is maybe through the noradrenergic stimulation?
A recent paper in Nature (Chouchani, Kazak et al - Nature, 532: 103 - here) shows evidence that the cold-induced thermogenesis in the BAT (brown adipose tissue), a process mediated by a well known protein - the uncoupling protein 1 (UCP1), which dissipates the proton gradient across the inner mitochondrial membrane, is, in fact, activated by ROS. The mitochondrial free radicals induce thiol oxidation (thiols always being quite sensitive to the redox potential), targeting in particular a cysteine moiety(Cys 253) in the UCP1 protein, and this oxidation is associated with the activation of the UCP1-dependent termogenic respiration.
(panel h from their fig. 4, describing the activation process; with the added information that the process is activated by adrenergic stimulation, something only briefly address in the paper). As per usual with the current Nature papers, a lot of data is not presented in the print version, but available as an Extended Data add-on.
The import at and crucial piece of evidence is that when MitoQ is used (a novel, magic drug, used in human clinical trials, with a powerful antioxidant activity, localised specifically to the mitochondria - see this 2012 review (open access)), and thus when the ROS production in the mitochondria is reduced, the thermogenesis (and the associated oxygen-consumption) is reduced.
Certainly, there are a number of important questions that need answering starting with how does cold triggers the specific increase in ROS? One potential explanation is maybe through the noradrenergic stimulation?
Labels: free radicals, mitochondria, ROS
Monday, January 28, 2013
A Norwegian voice out of the blue
as in this Truth thing: truth
