Grant: Travel Awards - Institute Community Support

All the cells in our body need energy to be alive. Over 90% of the energy required in heart muscle cells is produced in cellular structures called mitochondria. Since damaged mitochondria can cause cell death and heart injury, cells have quality control mechanisms to identify and eliminate damaged mitochondria (mitophagy). Mitophagy is efficient in eliminating damaged mitochondria, but is relatively slow and requires a lot of energy. Recently, our colleagues have discovered a new quality control mechanism that allows only the damaged components of mitochondria to be removed. In this process, the damaged components are pinched off in spherical structures called mitochondrial-derived vesicles (MDVs). Experiments using cells grown in the lab have shown that MDV formation can occur very quickly. To date however, no one has shown MDV formation occurs in the whole heart. Using isolated heart cells, we showed that when mitochondria are exposed to various damage inducing chemicals they produce many MDV quality control vesicles. A common side effect in humans of doxorubicin (Doxo), a cancer chemotherapy drug, is heart injury. Knowing this, we treated mice with Doxo to examine the formation of MDVs. Although the mitochondria in Doxo-treated mice hearts produced significantly less energy, we found no differences in heart function between treated and non-treated mouse hearts when we used an imaging technique to evaluate mechanical heart function (echocardiography). We also used electron microscopy (a very high resolution microscope) and saw an increase in the number of vesicles in hearts from Doxo-treated mice. Our study is the first to show that this new mechanism of mitochondrial quality control happens in the heart in response to stressors, such as the chemotherapeutic drug Doxo. This new cellular mechanism of mitochondrial protection is very important in the heart and can be, in the future, a new target for drugs protecting heart function and preventing heart injury.