The paternal mitochondria are destroyed by the egg just a few minutes after fertilization (Illustrative Image Infobae)
* This content was produced by experts from the Weizmann Institute of Science, one of the world’s leading centers for multidisciplinary basic research in the field of natural and exact sciences, located in the city of Rehovot, Israel.
A few minutes after the fertilizationhe egg of a fruit fly becomes the scene of a battle of the sexes. The Egg attacks and destroys the cellular “power plants,” or mitochondria, of the sperm that had fertilized it, so that only its own mitochondria remain. These findings from a new study by the Weizmann Institute of Science, published in Nature Communications could provide information on advanced fertilization treatments and shed light on a long-standing mystery: How and why do we inherit all our mitochondria from our mothers?
Las paternal mitochondria disappear shortly after fertilization in virtually all species, from sexually reproducing plants to fungi and insects and mammals, including humans. One theory holds that paternal mitochondria simply are diluted in maternal mitochondria, which are much more abundant, but another suggests that the egg actively eliminates them.
About a decade ago, Professor’s laboratory Searching for the Hand in it Weizmann Department of Molecular Genetics provided crucial evidence in favor of the theory of active elimination. The new study, led by PhD student Sharon Ben-Hurreveals the molecular details of this elimination, showing that the egg releases a deliberate attack and directed at the sperm mitochondria.
“It is possible that paternal mitochondria contain harmful components, “But they could also contain certain gifts from the father,” says Arama. “Either way, their decomposition could have a crucial impact on embryonic development.”
In preparation for destruction, the parental mitochondria of a fruit fly (green) are engulfed by clusters of vesicles called multivesicular bodies (magenta) that are coated with the protein Rubicon (Weizmann Institute of Science)
The sperm of the fruit fly, or Drosophila, is one of the largest in nature, making it an excellent model for these studies. Its mitochondria are not scattered, but fused along its tail into a single elongated structure. However, the fruit fly egg, as the team demonstrated, manages to destroy even this large formation.
Ben-Hur and his colleagues discovered that as soon as the sperm penetrates the egg, it is received by swarms of clusters of vesicles. In a manner that is obviously intentional and preprogrammed, these clusters immediately fuse to form a vesicular sheath that covers the entire length of the sperm tail. The mitochondrial structure of sperm tail breaks downwith pod and all, in smaller pieces.
After studying thousands of fruit fly embryos, Ben-Hur and his team were surprised to discover that the vesicles that form the sheath contain molecules involved in the innate immunity. Further research showed that the outer surface of the vesicular sheaths harbors large amounts of a protein called Rubicon, which is known to play a role in an immune pathway called LC3-associated phagocytosis or, for short, LAPwhich is known to work against invading microbes.
This discovery led researchers to decipher the entire pathway involved in mitochondrial degradation and reveal that it is indeed similar to LAP. Moreover, just as occurs within immune cells attacking microbes, the final step of LAP in the egg involves the lysosome recruitment, the cell’s recycling organelles, which complete the degradation of mitochondria.
The paternal mitochondria of a fruit fly (magenta) are clearly visible in the egg several minutes after it is laid (top left), but are completely destroyed within an hour (top, second from left). In a mutant fly lacking the Rubicon protein (bottom left), these mitochondria are not destroyed, even 1, 2, or 3 hours after the egg is laid (bottom row, second, third, and fourth from left) (Weizmann Institute of Science)
“We discovered that the egg repurposes an innate immunity pathway to destroy paternal mitochondria. In a way, it treats them as dangerous intruders”, says Ben-Hur. This discovery of the egg’s use of antimicrobial mechanisms fits with the hypothesis predominant over the primordial origins of mitochondria: in the ancient past, mitochondria could have started as bacteria that invaded the cells of a higher organism and stayed because the invasion was beneficial to both parties.
By explaining how the egg manages the destruction of structures as enormous as the fruit fly’s paternal mitochondria, the study could open a new direction of research in cell biology. Its findings could guide the search for hitherto unknown ways in which mitochondria cells degrade large structuressuch as entire organelles damaged.
The study could also offer new clues about Why is it necessary to destroy paternal mitochondria?. A common explanation relates to the cell’s need to maintain compatibility between its two genomes: one in the nucleus, which results from a fusion of maternal and paternal DNAand another, different one, in the mitochondria. According to this explanation, such compatibility should be easier to achieve when all mitochondria carry only maternal DNA, since too many different DNAs could collide. However, that might not be the whole story. Paternal mitochondria are vastly outnumbered by maternal ones, and their decay, in both fruit flies and humans, occurs long after their DNA has been removed.
(izq.) Dra. Keren Yacobi-Sharon, Shoshana Sernik, Prof. Eli Arama, Sharon Ben-Hur, Dr. Eyal Schejter and Dra. Alina Kolpakova (Instituto Weizmann de Ciencias)
“The fact that the egg cell resorts to surprisingly aggressive mechanisms to destroy paternal mitochondria suggests an urgency,” says Arama. “One possible reason is that these mitochondria could contain certain non-DNA components, such as RNA, that are harmful to the embryo, or, on the other hand, small non-genetic molecules that are released thanks to the destruction of mitochondria and could be vital for the development of the embryo.” In fact, when Ben-Hur created mutant fly embryos without the Rubicon protein, these embryos did not destroy the paternal mitochondria and did not develop properly.
The paternal mitochondria of humans and other mammals are destroyed through the same mechanisms as in fruit flies? Certain similarities have already emerged, including the expression of the LC3 molecule in the paternal mitochondria and the presence of clusters of vesicles in the vicinity of the sperm tail of mammals after fertilization.
If these similarities are confirmed in further studies, they could help improve state-of-the-art fertility treatmentsFor example, in a common technique of FIVa single sperm is injected into the egg to increase the chance of fertilization, rather than exposing the egg to multiple sperm in a test tube.
The attack of the egg simulates the immune pathway called LC3-associated phagocytosis (EFE/Bienvenido Velasco/Archive)
However, evidence from other areas of cell biology suggests that an injected sperm may lack the markers necessary for the destruction of its mitochondria, markers that it would have acquired if it had penetrated the egg spontaneously. The addition of these markers could potentially contribute to the success of the treatment.
Other fertility treatments involve the replacement of the egg’s mitochondria with those from a donor, for example, when maternal mitochondria are known to carry a disease-causing mutation. In such cases, understanding the mechanisms of mitochondrial destruction may help ensure that the donor’s mitochondria integrate correctly into the fertilized egg.
The study also involved Shoshana Sernik, Sara Afar, Dr. Alina Kolpakova, Dr. Yoav Politi, Dr. Liron Gal, Dr. Anat Florentin, Prof. Shmuel Pietrokovski, Dr. Eyal Schejter, and Dr. Keren Yacobi-Sharon from the Department of Molecular Genetics; Ofra Golani and Dr. Ehud Sivan from the Department of Life Sciences Core Facilities; Dr. Nili Dezorella from the Department of Chemical Research Support; and Dr. David Morgenstern from the Nancy and Stephen Grand Israel National Center for Personalized Medicine.
