Inhibiting mitochondrial fission protects the heart against ischemia/reperfusion injury.

Abstract

BACKGROUND: Whether alterations in mitochondrial morphology affect the susceptibility of the heart to ischemia/reperfusion injury is unknown. We hypothesized that modulating mitochondrial morphology protects the heart against ischemia/reperfusion injury. METHODS AND RESULTS: In response to ischemia, mitochondria in HL-1 cells (a cardiac-derived cell line) undergo fragmentation, a process that is dependent on the mitochondrial fission protein dynamin-related protein 1 (Drp1). Transfection of HL-1 cells with the mitochondrial fusion proteins mitofusin 1 or 2 or with Drp1(K38A), a dominant-negative mutant form of Drp1, increased the percentage of cells containing elongated mitochondria (65+/-4%..