Humanin directly protects cardiac mitochondria against dysfunction initiated by oxidative stress by decreasing complex I activity.

Humanin (HN) is an endogenous peptide that exerts cytoprotection against oxidative stress and apoptosis. We recently reported that Humanin analogue (HNG) pretreatment can reduce reactive oxygen species production in the heart subjected to ischemia/reperfusion (I/R) injury via attenuating mitochondrial dysfunction. However, it is unclear if HNG has direct effects on mitochondrial function against oxidative stress. Thus, we sought to determine the effects of HNG on mitochondrial function under hydrogen peroxide (H2O2) induced oxidative stress in isolated cardiac mitochondria. We found that HNG has direct protective effects on cardiac mitochondrial function against H2O2 induced oxidative stress through decreasing complex I activity.