Mom's eggs execute Dad's mitochondria.

In "Hamlet," Rosencrantz and Guildenstern deliver a letter to the rulers of England that carries the ill-fated duo's own death sentence. Perhaps Shakespeare knew a bit about reproductive biology.

Scientists have now found that during a sperm's creation, its mitochondria--energy-producing units that power all cells--acquire molecular tags that mark them for destruction once the sperm fertilizes an egg. This death sentence, a protein called ubiquitin, may explain why mammals inherit the DNA within mitochondria only from their mothers, a biological curiosity geneticists have used to trace human evolution (SN: 2/6/99, p. 88). The finding may also have implications for the safety of reproductive technologies, such as cloning, that introduce foreign mitochondria into an egg.

"If this is all correct, it's quite exciting," says mitochondrial geneticist Eric Schon of Columbia University College of Physicians and Surgeons in New York.

Many biologists used to believe, and some textbooks continue to say, that paternal mitochondria never get into the egg. That's a myth, however (SN: 1/25/97, p. 58).

"There is this paradox. We get all of our mitochondria from our mother, but our father's sperm mitochondria do enter the egg," says Gerald Schatten of the Oregon Health Sciences University in Beaverton.

Two theories arose to resolve the paradox. One suggests that the few-dozen mitochondria from sperm become undetectable once they're diluted among the 100,000 or so egg mitochondria. The second holds that a fertilized egg destroys sperm mitochondria within its first few cell divisions.

Schatten's colleague Peter Sutovsky discovered evidence for the latter process when he found that sperm maturing in the reproductive tract of male monkeys had mitochondria marked with ubiquitin, which cells use to tag molecules and organelles for recycling. This tag persists when the sperm fertilize eggs, the investigators reported in the Nov. 25, 1999 NATURE. Also, as they revealed last month at the meeting of the American Society for Cell Biology in Washington, D.C., injecting ubiquitin-blocking antibodies into fertilized eggs allowed paternal mitochondria to survive.

Sperm require energy from mitochondria to journey to an egg and fertilize it, Schatten notes. "They're not destroyed until they get into the egg cytoplasm, which would allow them to do all the work they need to do," he says.

The scientists continue to investigate how sperm label their mitochondria with ubiquitin and why sperm don't destroy their own tagged mitochondria.

Then, there's the oddity of cross-species mitochondrial inheritance. Sperm mitochondria sometimes avoid destruction when two different species of mice mate, and Schatten's team has shown this also holds true in cattle. It's hard to understand how an egg distinguishes between paternal mitochondria of closely related species, says Schon.

When paternal mitochondria escape destruction in normal mating, the resulting embryo may suffer. Schatten notes that a colleague has found sperm mitochondria in some defective embryos from infertility clinics.

The success of cloning may depend on an egg's ability to destroy foreign mitochondria. In the technique used to create Dolly the sheep, an egg gets mitochondria along with the nucleus from a donor cell. Those mitochondria ultimately disappear, notes Schon.