Myocardial infarction (MI) and heart failure (HF)—the leading causes of mortality world-wide—involve the metabolic dysfunction and death of heart-muscle cells. Two cell organelles are central to these processes: mitochondria and sarcoplasmic reticulum (SR), the specialized endoplasmic reticulum of cardiac-muscle cells that stores and releases calcium. The National Heart, Lung, and Blood Institute has awarded Richard N. Kitsis, M.D., a four-year, $2.5 million grant to study interactions between mitochondria, SR, and mitofusins—intracellular proteins that connect mitochondria with each other and to the SR.

Using peptides and small molecules that alter the shape of mitofusins, Dr. Kitsis and colleagues have found they can change the distance between mitochondria and SR, thereby influencing the transfer of calcium from SR to mitochondria. Specifically, mitofusin activators facilitate calcium transfer by bringing mitochondria and SR closer together, while mitofusin inhibitors do the opposite. The researchers will explore whether mitofusin inhibitors can help to reduce cell death during MI and, conversely, whether mitofusin activators can help to increase cardiac energy production in HF.

Dr. Kitsis is professor of medicine, of cell biology, the Dr. Gerald and Myra Dorros Chair in Cardiovascular Disease, and is the director of the Wilf Family Cardiovascular Research Institute at Einstein. (R01HL159062)