Post-translational modifications upon mitochondrial dysfunction in heart failure

Open in new tabDownload slide Proposed mechanism of 4-HNE generation by mitochondrial dysfunction, leading to inhibition of the RNase enzyme Dicer. Dicer generates non-coding mature miRNAs by the cleavage of precursor pre-miRNAs into mature miRNAs. miRNAs play a key role in several cardiac-related processes and, by blocking of Dicer, these miRNAs are dysregulated which leads to dysfunctional myocardial tissue. Stimulating ALDH2 via, for example, Alda-1, lowers the accumulation of 4-HNE and its inhibitory role on Dicer and miRNA generation, and thereby normalizes myocardial function.