NATURE
The high levels of tissue-damaging reactive oxygen species that arise during a stroke or heart attack have been shown to be generated through the accumulation of the metabolic intermediate succinate.
When a stroke or a heart attack strikes, the tissue injury that occurs can be devastating. This damage to the brain or heart is a result of an initial starving of oxygen owing to blocked blood flow, followed by reoxygenation once blood flow is restored. Ischaemia reperfusion (IR) injury, as it is called, is a major health burden, and there are very few options to prevent it. In a paper published on Nature's website today, Chouchani and colleagues1 present a finding that might inspire a new therapeutic approach. They reveal that succinate, an intermediate molecule normally formed during cellular respiration, is consistently elevated in ischaemic tissues, and that preventing this elevation is remarkably protective against IR injury in mouse models of stroke and heart attack. These findings add to those from other studies implicating succinate as an injurious metabolite, the limitation of which might have clinical utility.
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