Journal
NATURE
Volume 607, Issue 7920, Pages 756-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-022-04979-5
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Funding
- Instituto de Salud Carlos III [PT17/0019]
- European Regional Development Fund
- MINECO [BFU2017-89373-P]
- European Research Council Starting Grant [DORMANTOOCYTE -759107]
- Spanish Ministry of Science and Innovation
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Oocytes evade the negative effects of reactive oxygen species (ROS) by eliminating complex I in the mitochondrial electron transport chain. Early oocytes have low levels of complex I and an active mitochondrial unfolded protein response. This suppression of complex I represents a strategy for maintaining biological activity while achieving longevity.
Oocytes form before birth and remain viable for several decades before fertilization. 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 age. Reactive oxygen species (ROS) produced as by-products of mitochondrial activity are associated with lower rates of fertilization and embryo survival. 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.
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