Where have all dad's mitochondria gone?
It’s common knowledge that all organisms inherit their mitochondria – a cell’s “power plant” – from their mothers. But what happens to all the father’s mitochondria? A new theory may explain some of the failure rate in IVF.
Surprisingly, how and why a father's mitochondria are prevented from getting passed on to their offspring is still a mystery. The only thing that is certain is that it must be a compelling reason as all paternal mitochondria are 'missing' as a conserved (preserved) phenomenon throughout evolution.
Now, Dr. Eli Arama and a team in the Weizmann Institute’s Molecular Genetics Department have discovered special cellular vesicles that originate in the female fruit flies’ egg which actively seek out and destroy the father’s mitochondria upon fertilization.
This study, recently published in Development Cell, may help shed light on prevailing theories.
One theory is that paternal mitochondria are selectively “eaten” by a system known as autophagy, in which vesicles (which look like bubbles and are called autophagosomes) engulf a cell’s unwanted structures to destroy them. But the autophagy study was only conducted on the worm C. elegans whose sperm do not have the long, “head” and “tail” structures of both mammals and fruit-flies.
The mammal and fruit-fly sperm tail is either made up of mitochondria, or mitochondria are in a long tube attached to, or coiled around, the tail’s skeletal structure. How would a tiny autophagosome bubble engulf the large 2 mm long mitochondria of a fruit fly?
A second theory thinks that in mice the absence of paternal mitochondria is due to their being diluted in a sea of maternal mitochondria. But this doesn't explain why certain autophagy gene markers can still be detected on paternal mitochondria after fertilization.
Weizmann's team with the assistance of professor Zvulun Elazar's group, found a new explanation.
Cellular vesicles already existing in fruit fly eggs are 'magnetically' attracted to entering sperm.
These vesicles proceed to disintegrate the sperm’s outer membrane separating the mitochondria from the tail. The tail is then cut into smaller pieces and “devoured” by conventional autophagy.
Close observation reveals the "devouring vesicles" were not autophagosomes, but a different type of vesicle carrying autophagy markers. Arama: “We were not witnessing classic autophagy machinery. These structures were too large and morphologically distinct to be typical autophagosomes.”
The team’s findings suggest that the egg’s special cellular vesicles represent a new system — a unique combination of three separate biological steps whose paths have diverged from their classic functions.
These new discoveries, which the scientists believe exist in other organisms with sperm that have long tails (flagella), may help explain why only a quarter of IVF pregnancies carry to term.
It may be that the IVF procedure somehow overwhelms the egg's ability to destroy paternal mitochondria.
•Drosophila utilizes egg-derived paternal mitochondrial destruction (PMD) mechanisms
•PMD is mediated by a network of multivesicular body-like vesicles (MVBs)
•MVB clusters with endocytic/autophagic pathway features mediate sperm breakdown
•PMD requires p62 and involves sperm mitochondrial ubiquitination independent of Parkin
Almost all animals contain mitochondria of maternal origin only, but the exact mechanisms underlying this phenomenon are still vague. We investigated the fate of Drosophila paternal mitochondria after fertilization. We demonstrate that the sperm mitochondrial derivative (MD) is rapidly eliminated in a stereotypical process dubbed paternal mitochondrial destruction (PMD). PMD is initiated by a network of vesicles resembling multivesicular bodies and displaying common features of the endocytic and autophagic pathways. These vesicles associate with the sperm tail and mediate the disintegration of its plasma membrane. Subsequently, the MD separates from the axoneme and breaks into smaller fragments, which are then sequestered by autophagosomes for degradation in lysosomes. We further provide evidence for the involvement of the ubiquitin pathway and the autophagy receptor p62 in this process. Finally, we show that the ubiquitin ligase Parkin is not involved in PMD, implying a divergence from the autophagic pathway of damaged mitochondria.
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