Journal Article

Internalization of isolated functional mitochondria: involvement of macropinocytosis

Gojo, Satoshi, Kami, Daisuke, Matoba, Satoaki, Kitani, Tomoya

2014

Overview

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.

• Publisher: John Wiley & Sons, Inc,Blackwell Publishing Ltd
• Subject: Adenosine triphosphate / Animals / Cell Survival / Cell viability / Cells, Cultured / Cervix Uteri - cytology / Cervix Uteri - physiology / DNA, Mitochondrial - genetics / Electron transport / Endometrium / Endometrium - cytology / Endometrium - physiology / Energy Metabolism / Experiments / Female / Flow Cytometry / Heart attacks / Humans / Imaging, Three-Dimensional / Immunoelectron microscopy / Internalization / Localization / macropinocytosis / Mesenchyme / Mesoderm - cytology / Mesoderm - physiology / Microscopy / Microscopy, Confocal / Microscopy, Immunoelectron / Mitochondria / Mitochondria - metabolism / Mitochondria - transplantation / Mitochondria - ultrastructure / Mitochondrial DNA / mitochondrial transfer / Myocytes, Cardiac - cytology / Myocytes, Cardiac - physiology / Original / Pinocytosis / Polymerase chain reaction / Proteins / Rats / Real-Time Polymerase Chain Reaction / Respiration / rho0 cells / Studies / Uterus