title: Actin-dependent mitochondrial internalization in cardiomyocytes: evidence for rescue of mitochondrial function.
abstract: Previously, we have demonstrated that the transplantation of viable, structurally intact, respiration competent mitochondria into the ischemic myocardium during early reperfusion significantly enhanced cardioprotection by decreasing myocellular damage and enhancing functional recovery. Our in vitro and in vivo studies established that autologous mitochondria are internalized into cardiomyocytes following transplantation; however, the mechanism(s) modulating internalization of these organelles were unknown. Here, we show that internalization of mitochondria occurs through actin-dependent endocytosis and rescues cell function by increasing ATP content and oxygen consumption rates. We also show that internalized mitochondria replace depleted mitochondrial (mt)DNA. These results describe the mechanism for internalization of mitochondria within host cells and provide a basis for novel therapeutic interventions allowing for the rescue and replacement of damaged or impaired mitochondria.
authors: Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32607, USA.
authors: Christina A
authors: CA
authors: Pacak
authors: Division of Cardiac Surgery, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors: Janine M
authors: JM
authors: Preble
authors: Division of Cardiac Surgery, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors: Hiroshi
authors: H
authors: Kondo
authors: Universitat Leipzig, Molekulare Zelltherapie, Biotechnologisch-Biomedizinisches Zentrum, 04103 Leipzig, Germany.
authors: Peter
authors: P
authors: Seibel
authors: Division of Cardiac Surgery, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA Harvard Medical School, Boston, MA 02115, USA.
authors: Sidney
authors: S
authors: Levitsky
authors: Harvard Medical School, Boston, MA 02115, USA Division of Cardiac Surgery, Boston Children's Hospital, Boston, MA 02115, USA.
authors: Pedro J
authors: PJ
authors: Del Nido
authors: Harvard Medical School, Boston, MA 02115, USA Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
authors: Douglas B
authors: DB
authors: Cowan
authors: Division of Cardiac Surgery, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA Harvard Medical School, Boston, MA 02115, USA Division of Cardiac Surgery, Boston Children's Hospital, Boston, MA 02115, USA james_mccully@hms.harvard.edu.
authors: James D
authors: JD
authors: McCully
keywords: Cardioprotection; Endocytosis; Mitochondria; Mitochondrial DNA; Transplantation