Mitochondrial transfer between cells can rescue aerobic respiration. (Open access paper!) This article came to my attention yesterday as I was browsing the Journal of Cell Biology (content open access after 6 months) and found it covered in the Research Roundup. Dr. Prockop said that he had been viewing bone marrow stem cells and noticed they seemed very "social," reaching out cytoplasmic arms to touch adjacent cells and then backing away. He also knew that the addition of stem cells to damaged heart cells can help return function to the heart cells, and that damage to mitochondria in these heart cells is significant. So he came up with what he said was a "far-out" idea that stem cells might actually transfer mitochondria to other cells. He decided to investigate this, but if it didn't pan out he was planning on never telling anyone they had even considered it. They obtained a cell line and nuked it with ethidium bromide, a DNA-intercalating mutagen, to destroy the mitochondrial DNA. Then they did a series of experiments to confirm that the cells could not undergo aerobic respiration, the mitochondrial DNA was heavily damaged, and mitochondrial proteins were not being made. The cells were cultured in media containing pyruvate and uridine to allow anaerobic respiration and fibroblasts or bone marrow stem cells were added. After co-culture the damaged cells regained the ability to carry out aerobic respiration. The cells were cloned by limiting dilution and examined. The mitochondrial DNA in the cells was demonstrated to be identical to that of the donor cells, except in one case in which the original mitochondrial DNA persisted in addition to donor DNA. The researchers ruled out passive transfer by coculturing with platelets and by the addition of mitochondria fraction extract. They ruled out cell fusion by determining that no donor nuclear DNA was present in the restored clones. Finally, they managed to record the interaction of a stem cell with two damaged cells in non-permissive (no pyruvate or uridine, thus no anaerobic respiration) media. The damaged cells are devoid of ATP and senescent. The stem cell reached out a cytoplasmic arm to one damaged cell, and it shortly thereafter divided, indicating return of aerobic respiration. On the snapshots included in the paper you can see the mitochondrial cytoskeletal network streaming out towards the second cell. The researchers were unfortunately unable to catch mitochondria being transferred, so it is still possible that it is mitochrondrial DNA transferring and returning function. However, this is even more "far-out" than the idea of mitochondrial transfer because it would require copying the mitochondrial genome, exporting to the cytoplasm, transferring to the second cell, and importing into the damaged mitochondrion. Additionally, there is some evidence of vesicular transfer as in one experiment stem cells were observed to shed vesicles containing mitochondria, and in one case they were observed to stick to the membrane of another cell, although they were not observed being taken in.