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Redox modification of ryanodine receptors by mitochondria‐derived reactive oxygen species contributes to aberrant Ca2+ handling in ageing rabbit hearts

•  Ageing is associated with increased risk of sudden cardiac death due to malignant arrhythmias. •  Shortened refractoriness of Ca2+ release due to increased activity of Ca2+ release channels (RyRs) is recognized as an important contributor to cardiac‐triggered arrhythmias. However, molecular mechanisms of RyR dysfunction and its contribution to arrhythmias in ageing remain to be examined. •  Using ventricular myocytes isolated from old rabbit hearts we demonstrate that age‐associated increase in rate of production of reactive oxygen species (ROS) by mitochondria leads to the thiol‐oxidation of RyRs, which underlies the hyperactivity of the channels and thus shortened refractoriness of Ca2+ release in cardiomyocytes from the ageing heart. Mitochondria‐specific scavenging of ROS in old myocytes restored the redox status of RyRs, reducing SR Ca2+ leak and arrhythmogenic spontaneous Ca2+ waves. •  We conclude that increased ROS production by mitochondria contributes to age‐associated increased risk of stress‐induced arrhythmia and sudden cardiac death through thiol‐modifications of RyRs.