New insights into mitochondrial quality control in anthracycline-induced cardiotoxicity: molecular mechanisms, therapeutic targets, and natural products

Figure 1. Molecular mechanisms of AIC. The intricate pathological mechanisms underlying AIC encompass extensive damage to diverse cardiac cell types, notably cardiomyocytes, macrophages, fibroblasts, and endothelial cells, among others. This cellular injury is characterized by the accumulation of reactive oxygen species, the impairment of mitochondria, and the inhibition of topoisomerases, collectively culminating in cell death, including apoptosis, necrosis, and pyroptosis.

Figure 2. Mitochondrial quality control mechanisms in heart. Dynamic changes and interactions of mitochondrial biogenesis, mitophagy, mitochondrial fission and fusion in the healthy heart. Ac: acetylation; P: phosphorylation; mtDNA: mitochondrial DNA; Ub: ubiquitin.

Figure 3. Evolution of mitochondrial quality control mechanisms in AIC. The temporal changes in mitochondrial biogenesis, mitophagy, mitochondrial fission and mitochondrial fusion occurred in the heart during the development of AIC, respectively, including the early stage at 1 week after DOX treatment, the middle stage at 9 weeks after DOX treatment, and the late stage at 15 weeks after DOX treatment. Upward arrows represent up-regulation, downward arrows represent down-regulation, and Ø represents no change.

Figure 4. Regulatory network of mitochondrial quality control mechanisms in AIC. The red downward arrow represents the inhibitory effect of anthracyclines, and the red upward arrow represents the activating effect of anthracyclines. A: acetylation; P: phosphorylation.