Actin-dependent mitochondrial internalization in cardiomyocytes: Evidence for rescue of mitochondrial function

Christina A. Pacak, Janine M. Preble, Hiroshi Kondo, Peter Seibel, Sidney Levitsky, Pedro J. Del Nido, Douglas B. Cowan, James D. McCully

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)622-626
Number of pages5
JournalBiology Open
Volume4
Issue number5
DOIs
StatePublished - May 15 2015
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health, National Heart Lung and Blood Institutes, Public Health Service Grant HL103642 (to JDM) and The Anesthesia Research Distinguished Trailblazer Award, Boston Children's Hospital (to CAP).

Funding Information:
This work was supported by the National Institutes of Health, National Heart Lung and Blood Institutes, Public Health Service Grant HL103642 (to JDM) and The Anesthesia Research Distinguished Trailblazer Award, Boston Children’s Hospital (to CAP).

Publisher Copyright:
© 2015, Company of Biologists Ltd. All rights reserved.

Keywords

  • Cardioprotection
  • Endocytosis
  • Mitochondria
  • Mitochondrial DNA
  • Transplantation

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