Another Demonstration of Cells Taking Up Whole Mitochondria

One of the several possible approaches to address the important issue of mitochondrial damage in aging, wherein cells are overtaken by malfunctioning mitochondria and cause harm to surrounding tissues as a result, is some combination of destroying the damaged mitochondria and replacing them with whole new mitochondria infused into the body. Conveniently, it turns out that cells will of their own initiative take up and adopt new mitochondria introduced into the nearby environment. A number of demonstrations of this process have been carried out in recent years, and here is another one:

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. 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.

Link: http://onlinelibrary.wiley.com/doi/10.1111/jcmm.12316/full

Comments

ok, works well in a petri dish. Inject some tagged mitochondria into a Pig and see how that works out.

Posted by: JohnD at October 1st, 2014 10:27 AM

This certainly looks easier than conducting gene therapy on every cell in the body (or even just the long lived cells of the body).

Pure layman speculation, but I guess the in petri dish results might be better than in an animal model because you have the target cells surrounded by a high concentration of fresh mitochondria. A living body might flush out extra cellular components like that. Still it might be possible to borrow some of the methods being developed in cancer drug deliver research to target the mitochondria to long lived cells in the body such as liposomes or dna origami cages.

As Reason points out though, assuming Aubrey de Grey's hypothesis of positive selection for mutant mitochondria, even in a cell successfully transfected with fresh mitochondria, the mutant mitochondria already in the cell would eventually take over again. So some way of killing or reducing these needs to be found (the allotopic expression of mitochondrial dna is preferable in this regard).

Posted by: Jim at October 1st, 2014 1:50 PM
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