Heart failure & cardiomyopathies
MicroRNA-195 Regulates Metabolism in Failing Myocardium Via Alterations in Sirtuin 3 Expression and Mitochondrial Protein Acetylation
Authors' conclusion
Altogether, these data suggest that increased levels of miR-195 in failing myocardium regulate a novel pathway that involves direct SIRT3 suppression and enzymatic inhibition via increased acetylation of PDH and ATP synthase that are essential for cardiac energy metabolism.
Study context
- Population
- Failing human myocardium; human cardiomyocyte-like AC16 cells; SIRT3-/- and miR-195 transgenic mice
Main finding
As reported in the abstract
- Failing human myocardium: miR-195 induced, SIRT3 expression decreased, global protein acetylation increased
- Acetylome: increased overall acetylation and specific lysine acetylation of pyruvate dehydrogenase (PDH) and ATP synthase
- miR-195 downregulates SIRT3 via direct 3'-UTR targeting
- Nicotinamide, SIRT3 siRNA knockdown or miR-195 overexpression enhanced PDH complex and ATP synthase acetylation, reducing their activity and impairing mitochondrial respiration
- SIRT3-/- and miR-195 transgenic mice: enhanced global protein acetylation incl. PDH complex and ATP synthase, with decreased enzymatic activity
Original publication
MicroRNA-195 Regulates Metabolism in Failing Myocardium Via Alterations in Sirtuin 3 Expression and Mitochondrial Protein Acetylation. Circulation. Published 12 January 2018. doi:10.
Summarised from the published abstract; every number is checked against it