Oocytes maintain ROS-free mitochondrial metabolism by suppressing complex I, 2022, Rodríguez-Nuevo et al

Abstract

Oocytes form before birth and remain viable for several decades before fertilization1. Although poor oocyte quality accounts for most female fertility problems, little is known about how oocytes maintain cellular fitness, or why their quality eventually declines with age2. Reactive oxygen species (ROS) produced as by-products of mitochondrial activity are associated with lower rates of fertilization and embryo survival3,4,5. Yet, how healthy oocytes balance essential mitochondrial activity with the production of ROS is unknown. Here we show that oocytes evade ROS by remodelling the mitochondrial electron transport chain through elimination of complex I. Combining live-cell imaging and proteomics in human and Xenopus oocytes, we find that early oocytes exhibit greatly reduced levels of complex I. This is accompanied by a highly active mitochondrial unfolded protein response, which is indicative of an imbalanced electron transport chain. Biochemical and functional assays confirm that complex I is neither assembled nor active in early oocytes. Thus, we report a physiological cell type without complex I in animals. Our findings also clarify why patients with complex-I-related hereditary mitochondrial diseases do not experience subfertility. Complex I suppression represents an evolutionarily conserved strategy that allows longevity while maintaining biological activity in long-lived oocytes.

Open access, https://www.nature.com/articles/s41586-022-04979-5

 

Eggs can survive decades without signs of aging. Now, scientists may know why

"Mitochondria power the cell by taking electrons and using them to make a cellular fuel called ATP, through a process known as oxidative phosphorylation. It doesn’t happen all at once, but in a series of linked steps involving five protein complexes. Complex I is the largest of these molecular machines and the first to accept electrons.

“It’s considered to be the gatekeeper of this process,” Böke told STAT via email. So she was surprised to find that in studies of human and frog oocytes, the mitochondrial genes that produce Complex I were turned off. Only one other multicellular organism is known to be able to exist without it — the parasitic mistletoe.

By skipping Complex I, primordial oocytes are able to maintain a super-low energy state, kind of like standby mode, while removing a major source of electron leakage, and therefore damage from free radicals."

https://www.statnews.com/2022/07/20/why-eggs-can-survive-decades-without-signs-of-aging/