Prohibitin1 maintains mitochondrial quality in isoproterenol-induced cardiac hypertrophy in H9C2 cells

Background InformationVarious types of stress initially induce a state of cardiac hypertrophy (CH) in the heart. But, persistent escalation of cardiac stress leads to progression from an adaptive physiological to a maladaptive pathological state. So, elucidating molecular mechanisms that can attenuate CH is imperative in developing cardiac therapies. Previously, we showed that Prohibitin1 (PHB1) has a protective role in CH-induced oxidative stress. Nevertheless, it is unclear how PHB1, a mitochondrial protein, has a protective role in CH. Therefore, we hypothesized that PHB1 maintains mitochondrial quality in CH. To test this hypothesis, we used Isoproterenol (ISO) to induce CH in H9C2 cells overexpressing PHB1 and elucidated mitochondrial quality control pathways. ResultsWe found that overexpressing PHB1 attenuates ISO-induced CH and restores mitochondrial morphology in H9C2 cells. In addition, PHB1 blocks the pro-hypertrophic IGF1R/AKT pathway and restores the mitochondrial membrane polarization in ISO-treated cells. We observed that overexpressing PHB1 promotes mitochondrial biogenesis, improves mitochondrial respiratory capacity, and triggers mitophagy. ConclusionWe conclude that PHB1 maintains mitochondrial quality in ISO-induced CH in H9C2 cells. SignificanceBased on our results, we suggest that small molecules that induce PHB1 in cardiac cells may prove beneficial in developing cardiac therapies.

Automated summary

The research found that overexpression of PHB1 can alleviate and restore the oxidative stress and mitochondrial morphology changes induced by cardiac hypertrophy. Further experimental results showed that overexpressing PHB1 can maintain mitochondrial quality through blocking pro-hypertrophic pathway, restoring mitochondrial membrane polarization, promoting mitochondrial biogenesis, improving mitochondrial respiratory capacity, and triggering mitophagy.