TMEM65 regulates and is required for NCLX-dependent mitochondrial calcium efflux

The mitochondrial sodium-calcium exchanger, NCLX, is a critical route of mCa2+ efflux in excitable tissues, such as the heart and brain, and animal models support NCLX as a promising therapeutic target to limit pathogenic mCa2+ overload. Dr. Elrod’s group from Temple University uncovered a novel mechanism underlying the regulation of NCLX activity that involves mitochondrial inner membrane protein TMEM65. As a binding partner of NCLX, TMEM65 enhances sodium-dependent mCa2+ efflux and homeostasis, preventing mCa2+ overload, cell death, and organ-level dysfunction.