Editorial Volume 15, Issue 9 pp 3226—3227

Figure 1. Autophagy enhancement attenuates proteasome dysfunction–mediated cardiotoxicity. Drosophila bears a heart-like structure and a circulatory system with developmental and functional homologies to the vertebrates' heart and circulation. Genetic heart-targeted proteasome dysfunction or exposure of flies to systemic anti-tumor therapeutic PIs triggers increased oxidative, proteotoxic and energetic stress in cardiac tissues resulting in (among others) mitochondrial perturbation, low energy levels and eventually severe cardiotoxicity. Although less studied, these consecutive events that trigger systemic toxicity and cardiac complications can be also seen in tumor patients treated with PIs, leading to therapy discontinuation and a negative survival outcome. As found in the fly model [6] proteasome dysfunction-mediated cardiotoxicity can be partially rescued by pharmacological co-treatment with autophagy activators such as metformin/rapamycin or by caloric restriction; in humans additional lifestyle adaptations (e.g. daily exercise) can be also beneficial.