Scientists at Michigan State University uncovered how developing sperm cells organize a molecular system essential for male fertility, revealing a nontraditional role for mitochondria — the structures best known as the cell’s energy producers. This work could ultimately help scientists better understand some causes of male infertility and the basic biology behind healthy sperm development.
Published in the journal Proceedings of the National Academy of Sciences, the study, which used mouse models, shows that mitochondria also act like cellular assembly platforms, gathering and organizing the molecular machinery needed to produce molecules called pachytene piRNAs, which are critical for sperm development.
Although pachytene piRNAs are known to be essential for male fertility, scientists have long struggled to understand how the system is physically organized inside cells.
“We found that mitochondria are doing much more than supplying energy,” said Chen Chen, professor in the Department of Animal Science at MSU and senior author of the study. “They are acting as organizational hubs that bring together the machinery needed for this small RNA-based fertility pathway to function properly.”
The researchers discovered that two proteins, known as MILI and MIWI, are guided to specific locations on the mitochondrial surface by different scaffold proteins. This careful organization allows sperm cells to assemble the machinery needed to produce pachytene piRNAs at the right place and time.
When the researchers removed one of the mitochondrial surface scaffold proteins, called ASZ1, the system largely collapsed. Cells lost the ability to properly produce most pachytene piRNAs, key cellular structures failed to form correctly, and sperm development stopped prematurely, leading to infertility in mice.
But the researchers also uncovered a striking finding.
Even after losing nearly all pachytene piRNAs, the cells could still suppress potentially harmful genetic elements known as transposons, which can damage DNA if left unchecked. That suggests most pachytene piRNAs may play broader and more complex roles in fertility than scientists previously understood.
“For a long time, people thought these molecules were mainly involved in protecting the genome,” Chen said. “What we’re seeing is that only a small amount may be needed for that job, while the majority may be involved in other important steps in sperm development that we are only beginning to understand.”
The study also revealed that after pachytene piRNAs are produced, the molecules move to other specialized structures inside the cell where they likely help direct later stages of sperm development. The findings provide new insight into how cells organize complicated biological systems in space and time.
“Without this organization, the whole system fails,” Chen said. “The cell has to carefully coordinate where these molecules go and when they interact.”
The study was supported by the National Institutes of Health and the U.S. Department of Agriculture
