LAUSR

The protein DDiT4L protects the heart from pathological hypertrophy by stimulating autophagy (Simonson et al. in 28 February 2017 issue). Abstract This Podcast features an interview with Saumya Das, senior author of a Research Article that appears in the 28 February 2017 issue of Science Signaling, about a protein that inhibits pathological cardiac hypertrophy in mice. Temporary increases in cardiac workload, such as those caused by exercise or pregnancy, induce physiological cardiac hypertrophy, a beneficial type of heart enlargement that is adaptive. However, a sustained increase in workload due to metabolic stress or uncontrolled high blood pressure induces pathological cardiac hypertrophy, which can contribute to heart failure. Simonson et al. found that expression of DNA-damage-inducible transcript 4-like (DDiT4L) increased during pathological hypertrophy, but not during physiological hypertrophy, in mice. DDiT4L promoted stress-induced autophagy in cardiomyocytes by inhibiting signaling through the mechanistic target of rapamycin complex 1 (mTORC1) and stimulating signaling through mTORC2. These findings suggest that targeting autophagy, which is important for cellular homeostasis but can be detrimental in excess, may be useful for treating some cardiovascular diseases. Listen to Podcast