Severe ER impairment in cardiomyocytes can eventually lead to cardiac dysfunction. The ER is the organelle that the researchers observed carrying out autophagy during drug-induced stress.
"Endoplasmic reticulum-selective autophagy could be a useful protective mechanism against drug-induced cardiotoxicity," explains first author Shun Nakagama."However, there is a lack of research showing the presence of ER-phagy in cardiomyocytes. We therefore aimed to determine whether ER-phagy is helping to protect the heart from drug-induced ER stress."
The researchers developed a novel ER-phagy monitoring system in cardiomyocytes to visualize the activation of ER-phagy and identify protein regulators that control selective autophagy in the presence of Dox-induced ER stress. Additionally, awas used to determine an accurate representation of the cardioprotective role of ER-phagy in mammals.
"Our results showed that ER-phagy indeed alleviates Dox-induced cardiomyopathy," says corresponding author Yasuhiro Maejima."We determined that Dox-induced ER-phagy was activated by the interplay between two protein regulators: cell-cycle progression gene 1 and TANK binding kinase 1. ER stress, caused by Dox, was exacerbated without this protein interaction, which then decreased cell survival.