Mitochondrial Lipid Peroxidation Initiates Rapid Accumulation of Lipofuscin in Cell Culture

It was shown that the enhancement of lipid peroxidation (LPO) in mitochondria of rat H9c2 cardiomyoblasts and human fibroblasts under the action of the cystine transport inhibitor erastin or the glutathione peroxidase-4 inhibitor RSL3 is accompanied by rapid (18 h) accumulation of lipofuscin. The mitochondria-targeted antioxidant SkQ1 and the redox mediator methylene blue, which prevents the formation of reactive oxygen species (ROS) in complex I of the mitochondrial respiratory chain, blocked both mitochondrial LPO and lipofuscin accumulation. These data indicate that mitochondrial LPO serves as a driving force for the accelerated accumulation of lipofuscin in cells. In isolated heart mitochondria, rapid (24 h) formation of lipofuscin was observed, which depended on the presence of iron ions, was significantly accelerated by ROS generated in complex I of the respiratory chain, and was blocked by SkQ1. The question of whether oxidized components of mitochondria serve as the initial material for lipofuscin formation in cells remains open. The obtained results give hope for the successful application of mitochondria-targeted compounds in the treatment of many diseases associated with excessive accumulation of lipofuscin.