Mitochondrial dynamics have been involved in cardiovascular diseases, particularly in ischemia-reperfusion process. While excessive mitochondrial fission has been described as pejorative, the role of fusion proteins (OPA1, MFN2) in this context remains uncertain.

To determine the effects of OPA1 (protein implicated in mitochondrial inner membrane fusion) deficiency on cardiac ischemia-reperfusion (I/R) injury.

We investigated cardiac structure and function (assessed by TTE) of OPA1+/– mutant mice (50% of OPA1 expression decreasing) and found that they displayed a significant alteration of left ventricular systolic function at 6 months, but were similar to Wild-type (WT) at 3 months. 3-month-old OPA1+/– mutant mice and theirs controls were then submitted to I/R in vivo (coronary artery ligature during 45 min/ 2h reperfusion) and ex vivo (30 min of global ischemia / 2h reperfusion). In vivo, infarct size was significantly higher in OPA1+/– mutant mice compared to WT group (43.2±4.1% vs. 28.4±3.5% respectively; p<0.01). Same results were observed in Langendorff model (71.1±3.2% vs. 59.6±8.5% respectively; p<0.05). No difference was observed in fission/fusion proteins expression, oxidative phosphorylation, apoptotic markers or mPTP function between mutant mice and WT after I/R. However, calcium transients were significantly lower in OPA1+/– mice suggesting an alteration of sarcoplasmic reticulum calcium capacity uptake.

Deficiency in the fusion protein OPA1 was associated with higher susceptibility to myocardial I/R injury. Physiopathological mechanisms seem to involve calcium transients modulation, but need further explorations.

The author hereby declares no conflict of interest