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Sci Rep. 2017 Dec 12;7(1):17450. doi: 10.1038/s41598-017-17813-0.

Transit and integration of extracellular mitochondria in human heart cells.

Author information

1
Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, 02115, Massachusetts, USA. douglas.cowan@childrens.harvard.edu.
2
Department of Anæsthesia, Harvard Medical School, Boston, 02115, Massachusetts, USA. douglas.cowan@childrens.harvard.edu.
3
Harvard Stem Cell Institute, Harvard University, Cambridge, 02138, Massachusetts, USA. douglas.cowan@childrens.harvard.edu.
4
Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, 02115, Massachusetts, USA.
5
Department of Anæsthesia, Harvard Medical School, Boston, 02115, Massachusetts, USA.
6
Department of Cardiac Surgery, Boston Children's Hospital, Boston, 02115, Massachusetts, USA.
7
Department of Surgery, Harvard Medical School, Boston, 02115, Massachusetts, USA.

Abstract

Tissue ischemia adversely affects the function of mitochondria, which results in impairment of oxidative phosphorylation and compromised recovery of the affected organ. The impact of ischemia on mitochondrial function has been extensively studied in the heart because of the morbidity and mortality associated with injury to this organ. As conventional methods to preserve cardiac cell viability and contractile function following ischemia are limited in their efficacy, we developed a unique approach to protect the heart by transplanting respiration-competent mitochondria to the injured region. Our previous animal experiments showed that transplantation of isolated mitochondria to ischemic heart tissue leads to decreases in cell death, increases in energy production, and improvements in contractile function. We also discovered that exogenously-derived mitochondria injected or perfused into ischemic hearts were rapidly internalised by cardiac cells. Here, we used three-dimensional super-resolution microscopy and transmission electron microscopy to determine the intracellular fate of endocytosed exogenous mitochondria in human iPS-derived cardiomyocytes and primary cardiac fibroblasts. We found isolated mitochondria are incorporated into cardiac cells within minutes and then transported to endosomes and lysosomes. The majority of exogenous mitochondria escape from these compartments and fuse with the endogenous mitochondrial network, while some of these organelles are degraded through hydrolysis.

PMID:
29234096
PMCID:
PMC5727261
DOI:
10.1038/s41598-017-17813-0
[Indexed for MEDLINE]
Free PMC Article

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