In a remarkable discovery, scientists show that blocking the action of a key
enzyme in mitochondria stops stem cells from developing into egg cells in fruit
flies.
Mitochondria play a vital role in stem cell development.
Mitochondria – tiny digestive systems found inside nearly every cell of the body – are
traditionally known for their vital role in generating energy for cells to function.
In the new study, published in Nature Cell Biology, a team led by researchers
from NYU Langone Medical Center, NY, shows that mitochondria’s role in the development of
stem cells is entirely distinct from that of producing energy for cell metabolism.
In their traditional role, mitochondria provide cells with units of energy in the form
of adenosine triphosphate (ATP). The chemical reaction that produces ATP relies on an
important enzyme called ATP synthase enzyme.
The new research shows that ATP synthase is also important for normal stem
cell development. The enzyme directly controls the growth and maintenance of “cristae” –
the wrinkled, folded membranes inside mitochondria – as the stem cells divide and form
the specific cell components of the female germ cell or egg.
Because ATP synthase energy production is common in all cells with a nucleus, the
researchers say it is very likely that what they have found in the fruit flies
experiments will be true of all mammals, including humans.
Blocking any of 13 key ATP synthase proteins stopped egg development
Senior investigator Ruth Lehmann, a cell biology professor at NYU Langone, says earlier
studies have discovered damaged or immature cristae in several animal species with faulty
ATP synthase, but this is the first study to show a link to stem cell development.
In their experiments, Prof. Lehmann and colleagues found blocking any of the 13 key
proteins linked to ATP synthase disrupted or stalled egg development in the fruit
flies.
They also found that blocking other enzymes involved in ATP production –
before ATP synthase steps in – did not damage egg development.
The study took 2 years as the team screened more than 8,000 fruit fly genes thought to
be involved in the development of stem cells that lead to egg or sperm. ATP synthase
stood out – they noticed how it remained active even when other enzymes involved in ATP
production were turned off.
Team plans to investigate whether mitochondria play any other vital roles
Prof. Lehmann explains how she and her colleagues will continue the research:
“Our team plans further investigations into precisely how ATP synthase
biologically controls cristae development, and whether other developmental roles are
influenced by mitochondria.”
Funds for the study came from the US National Cancer Institute and National Institute
of Child Health and Human Development, both parts of the National Institutes of Health.
Boehringer Ingelheim Fonds, and the American Cancer Society also supported the
study.
Mitochondria hit the headlines earlier this week because of a breakthrough study that
holds promise for families affected by potentially severe diseases caused by faulty
mitochondrial DNA that passes to children from their mothers.
The study, reported recently by Medical News Today, shows how a team used
enzymes as molecular scissors to edit mutated
mitochondrial DNA in female mice that went on to have healthy offspring with very low
levels of the targeted faulty DNA.
The Salk Institute team says if the editing technique works in humans, it will offer a
safer, simpler and more ethical alternative to three-parent IVF mitochondrial replacement therapy.