The Role of Mitochondrial Quality Control in Anthracycline-Induced Cardiotoxicity: From Bench to Bedside

Figure 3

Regulation mechanism of mitochondrial biogenesis. PGC1α is the central regulator of mitochondrial biogenesis. The upstream regulatory mechanisms of PGC1α include AMPK phosphorylation and SIRT1 deacetylation. PGC1α modulates the expression of antioxidant proteins such as superoxide dismutase and glutathione peroxidase. More importantly, PGC1α activates downstream transcription factors including NRF1/2, ERR-α, and PPAR, which transactivate nuclear genes related to mitochondrial protein import and assembly, mtDNA transcription, replication and translation, TCA cycle, and OXPHOS. Genomic information is transcribed into mRNAs in the nucleus and then translated into proteins via cytosolic ribosomes. Nuclear gene-encoded mitochondrial proteins are transported into mitochondria via the TIM/TOM complex and are finally involved in the process of supplying cellular energy: peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α), AMP-activated protein kinase (AMPK), Sirtuin 1 (SIRT1), nuclear respiratory factor 1/2 (NRF1/2), estrogen-related receptor alpha (ERR-α), peroxisome proliferator-activated receptors (PPARs), translocase of the inner membrane (TIM), translocase of the outer membrane (TOM), mitochondrial DNA (mtDNA), tricarboxylic acid (TCA), and oxidative phosphorylation (OXPHOS).