How ‘Idle’ Egg Cells Defend Their DNA From Damage by toxic proteins for decades

Amazing stuff! Wonders of life!

"Recently, in a study published in Cell, researchers discovered how mouse oocytes keep DNA safe from damaging proteins. The cells construct special compartments within themselves to temporarily sequester the proteins. Then, heeding a molecular signal, the storage units disperse all at once, practically vanishing along with their dangerous cargo. Thus cleaned, the oocyte is left to mature safely. ..."

"Oocytes are immature egg cells that develop in almost all female mammals before birth. The propagation of future generations depends on this finite reserve of cells surviving for many years without incurring damage. In mice, this can be a period of up to eighteen months, while in humans it can last almost half a century, the average time between birth and menopause. How the cells accomplish this remarkable feat of longevity has been a longstanding question. ..."

From the highlights and abstract:

"Highlights

• Mouse oocytes store protein aggregates in endolysosomal vesicular assemblies (ELVAs)

• ELVAs harbor endolysosomes, autophagosomes, and proteasomes in a liquid-like matrix

• ELVAs degrade aggregates upon oocyte maturation to promote healthy embryogenesis

• Retention of protein aggregates in the embryo leads to early embryonic arrest

Summary

Oocytes are among the longest-lived cells in the body and need to preserve their cytoplasm to support proper embryonic development. Protein aggregation is a major threat for intracellular homeostasis in long-lived cells. How oocytes cope with protein aggregation during their extended life is unknown. Here, we find that mouse oocytes accumulate protein aggregates in specialized compartments that we named endolysosomal vesicular assemblies (ELVAs). Combining live-cell imaging, electron microscopy, and proteomics, we found that ELVAs are non-membrane-bound compartments composed of endolysosomes, autophagosomes, and proteasomes held together by a protein matrix formed by RUFY1. Functional assays revealed that in immature oocytes, ELVAs sequester aggregated proteins, including TDP-43, and degrade them upon oocyte maturation. Inhibiting degradative activity in ELVAs leads to the accumulation of protein aggregates in the embryo and is detrimental for embryo survival. Thus, ELVAs represent a strategy to safeguard protein homeostasis in long-lived cells."

How ‘Idle’ Egg Cells Defend Their DNA From Damage | Quanta Magazine How do immature egg cells maintain genetic quality for decades before they mature? Scientists find unusual safeguards in this quiescent cell that may inform research into fertility.

How Oocytes Outsmart Toxic Proteins To Preserve Long-Term Female Fertility (original news release) How Oocytes Outsmart Toxic Proteins to Preserve Long-term Female Fertility

Mouse oocytes sequester aggregated proteins in degradative super-organelles

Graphical abstract