HEALTHY cells seem to have shown an amazing ability to breathe new life into damaged ones by rejuvenating their defunct mitochondria. It is an extraordinary and controversial claim. But if confirmed it could offer a way to prevent a range of harrowing metabolic diseases that affect millions of people.
Experts in mitochondrial research have yet to be convinced. They say the work purporting to show the effect has yet to be comprehensively peer-reviewed, and is so potentially ground-breaking that more evidence is needed.
Mitochondria carry their own DNA, separate from nuclear DNA, and provide the metabolic energy cells need to function properly. When the mitochondria are abnormal, or damaged, often by inherited defects in their DNA, they cause a range of debilitating diseases, which are often fatal in infancy. In the US alone, 4000 children are born each year with mitochondrial defects that can trigger diseases ranging from leukaemia and cerebral palsy to liver failure and blindness.
Advertisement
Now a team led by Darwin Prockop at Tulane University in New Orleans says it has discovered that mitochondrial DNA (mtDNA) from healthy cells can migrate into neighbouring cells with defective or non-existent mitochondria, even when the cells are not fused together. And by doing so, healthy cells can breathe life back into damaged ones.
The team used ethidium bromide to destroy all the mitochondria in lung cancer cells kept in the lab. When healthy cells, either bone marrow stem cells or skin cells called fibroblasts, were then placed alongside the cancer cells, some recovered. These rejuvenated cells contained mtDNA from their healthy neighbours, meaning they had either absorbed the genetic material or 鈥渢he healthy cell discharges a membrane-enclosed vessel containing mitochondria that the defective cell engulfs鈥�, Prockop told 快猫短视频.
The rejuvenated cells trebled the amount of oxygen they were consuming 鈥� a sign that the mitochondria had resumed work 鈥� and tripled their production of the energy molecule adenosine triphosphate (ATP). They also stopped accumulating the lactate waste products which clog up defective cells (Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0510511103).
鈥淩ejuvenated cells trebled the oxygen they were consuming, a sign that the mitochondria had resumed work鈥�
The medical implications of the discovery are huge. It raises the possibility of using healthy cells to correct defective mitochondria in patients with mitochondrial diseases, or even to identify and permanently correct such defects in an embryo. 鈥淲e are not just talking about a potential therapy, but maybe considering a cure,鈥� says Paul Preston, secretary of the UK Children鈥檚 Mitochondrial Disease Network charity based in Northwich, Cheshire.
However, researchers studying mitochondria are sceptical. It is very difficult to create cell cultures devoid of mtDNA, and the mtDNA in the rejuvenated cells could have survived the chemical purge or be the result of contamination, says Keshav Singh of the US Mitochondria Research Society, and editor-in-chief of the journal Mitochondrion. He and Bob Lightowlers of the Mitochondrial Research Group at the University of Newcastle upon Tyne, UK, say other scientists need to validate the work as soon as possible.
Prockop says his team thinks it has ruled out any contamination. But Lightowlers still has doubts. 鈥淚 can鈥檛 point to anything in the paper and say unequivocally: 鈥楾hat鈥檚 wrong鈥�,鈥� he says. 鈥淏ut extraordinary claims need to be extraordinarily convincing鈥nd people in the field will find it very difficult to believe.鈥�
