If you asked yourself why we only inherit the mitochondria from the mother, the answer is - the egg is the one that destroys the father's mitochondria very shortly after fertilization
Minutes after a sperm meets an egg in the fruit fly, the latter becomes the scene of an active struggle between the species. The fertilized egg attacks and destroys the mitochondrial organelles - the cellular "power plants" - of the sperm that enters it, just as if they were a foreign invader, leaving only its own mitochondria intact. These new findings of Weizmann Institute of Science scientists shed light on an ancient matriarchal mystery: why and how are all the mitochondrial organelles in our body a maternal inheritance?
In almost all species - from sexually reproducing plants, through fungi and insects to mammals, including humans - the father's mitochondrial organelles mysteriously disappear shortly after fertilization. According to one theory, these organelles disappear simply because they are null in sixty compared to the enormous number of mitochondrial organelles of the mother in the fertilized egg. However, there is also a widespread theory that holds that the egg eludes them on purpose.
About a decade ago, scientists in the laboratory of Prof. Eli Arma in the department of molecular genetics of the institute Evidence for the "The Secret Hand" Theory. Now in a new study, led by research student Sharon Ben-Hur, the scientists revealed the molecular details of this hand, and showed how the egg launches a directed and targeted attack against the mitochondria of the sperm cell.
"It is possible that the paternal organs contain harmful factors and are therefore destroyed - but it is also possible that they contain valuable dowry from the father", Prof. Arma intensifies the mystery. "One way or another, the breakdown of the father's mitochondria has a decisive effect on the further development of the fly."
Cross the Rubicon
Fruit fly sperm cells are particularly suitable for this type of research, as they are among the largest cells of their kind in nature. Also, their mitochondrial organelles are not scattered all over the cell but are located along the tail of the sperm and connected together into one long structure.
In the new study, Ben-Hur and her colleagues showed that as soon as a sperm cell penetrates the egg, it is preceded by swarms of bubbles that join forces and wrap the sperm's tail along its entire length. This well-orchestrated envelope leads to the breaking down of the mitochondrial structure located in the tail into smaller, easier-to-digest pieces.
In the next step, after examining thousands of fruit fly embryos, Ben-Hur and her partners were surprised to discover that the vesicles that wrap the tail of the sperm contain molecules identified with the innate immune system. Further tests revealed that the surface of the bubble shell contains particularly large amounts of Rubicon - a protein of the immune system known for its activity against invading bacteria.
Later, the scientists revealed the complete biochemical pathway of the breakdown of the paternal mitochondria in the egg and showed that it is indeed reminiscent of what happens in the cells of the immune system that engulf and kill bacteria. For example, just like in these cells, the last step in the mitochondria breakdown pathway in the fertilized egg is the recruitment of lysosomes - the organelles of the cell cycle - which complete the mitochondrial breakdown and digestion.
"We discovered that the egg pours new content into the biochemical pathway of the innate immune system with the aim of recruiting it to destroy the father's mitochondria. In fact, it can be said that she treats these organs like dangerous intruders," says Ben-Hur. These findings are also in line with the prevailing theory about the ancient origin of the mitochondria, according to which this organelle began its journey as a bacterium that invaded the cell of a more developed organism, saw that it was good and stayed to stay. This invasion benefited both sides and became an evolutionary reality.
But why does the egg bother so much to destroy the father's mitochondria? One possible explanation refers to the cell's need to produce compatibility between its two genomes: the genome in the nucleus, which is formed by a fusion between the father's and mother's DNA, and the mitochondrial genome, which is different from the one in the nucleus. According to this explanation, it is easier to achieve compatibility and harmony in the cell if all mitochondrial organelles carry the mother's DNA rather than the father's, as too many types of DNA can lead to collisions and malfunctions. But this may not be the whole story, because both in flies and in humans the DNA of the paternal mitochondria breaks down long before the mitochondria themselves break down.
"The fact that the egg uses such aggressive mechanisms to destroy the father's mitochondria indicates the urgency of the destruction," says Prof. Arma. "One possible explanation may be that the father's mitochondria contain components that are not DNA, for example RNA, which may harm the fetus - on the other hand, it is also possible that they contain small molecules that may benefit the development of the fetus, so it is worthwhile to break them down and utilize them." To examine this question, Ben-Hur created genetically engineered fly embryos that are unable to produce the Rubicon protein. The researchers showed that these embryos fail to destroy the father's mitochondria, and indeed their own development is impaired.
Are the paternal mitochondrial organelles also destroyed in humans using the same ancient mechanisms? There is evidence to suggest similarities in these processes along the evolutionary tree. For example, even in mammals, clusters of bubbles have been identified in the past near the tail of the sperm after fertilization of the egg.
Besides reflecting on the war of the sexes and solving the long-standing scientific mystery, if these similarities are validated in future studies, they may pave the way for the introduction of improvements in advanced fertility treatments, such as in vitro fertilization or treatments that include the replacement of the mother's mitochondria - for example following dangerous mutations - through egg donation.
Shoshana Sarnik, Sarah Afar, Dr. Alina Kolpakova, Dr. Yoav Foliti, Dr. Liron Gal, Dr. Anat Florentin, Prof. Shmuel Petrokovsky, Dr. Eyal Schechter and Dr. Karen Yacovi-Sharon also participated in the study. from the Department of Molecular Genetics; Ofra Golani and Dr. Ehud Sion from the Department of Life Sciences Research Infrastructures; Dr. Neely Dzorla from the Department of Chemical Research Infrastructures; and Dr. David Morgenstern from the Israeli National Center for Personalized Medicine for Nancy and Steven Grand.
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