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J Cell Mol Med. 2014 Aug;18(8):1694-703. doi: 10.1111/jcmm.12316. Epub 2014 Jun 9.

Internalization of isolated functional mitochondria: involvement of macropinocytosis.

Author information

1
Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University School of Medicine, Kyoto, Japan.

Abstract

In eukaryotic cells, mitochondrial dysfunction is associated with a variety of human diseases. Delivery of exogenous functional mitochondria into damaged cells has been proposed as a mechanism of cell transplant and physiological repair for damaged tissue. We here demonstrated that isolated mitochondria can be transferred into homogeneic and xenogeneic cells by simple co-incubation using genetically labelled mitochondria, and elucidated the mechanism and the effect of direct mitochondrial transfer. Intracellular localization of exogenous mitochondria was confirmed by PCR, real-time PCR, live fluorescence imaging, three-dimensional reconstruction imaging, continuous time-lapse microscopic observation, flow cytometric analysis and immunoelectron microscopy. Isolated homogeneic mitochondria were transferred into human uterine endometrial gland-derived mesenchymal cells in a dose-dependent manner. Moreover, mitochondrial transfer rescued the mitochondrial respiratory function and improved the cellular viability in mitochondrial DNA-depleted cells and these effects lasted several days. Finally, we discovered that mitochondrial internalization involves macropinocytosis. In conclusion, these data support direct transfer of exogenous mitochondria as a promising approach for the treatment of various diseases.

KEYWORDS:

macropinocytosis; mitochondrial transfer; rho0 cells

PMID:
24912369
PMCID:
PMC4190914
DOI:
10.1111/jcmm.12316
[Indexed for MEDLINE]
Free PMC Article

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