22 July 2022

Long hibernation

Eggs "sleep" for decades, suppressing the activity of mitochondria

Elizaveta Minina, PCR.news

In humans, oocytes in the ovaries are formed during intrauterine development and at the same time retain the ability to fertilize for about 50 years, despite a long period of rest. The authors of a new paper published in Nature (Rodríguez-Nuevo et al. Oocytes maintain ROS-free mitochondrial metabolism by suppressing complex I), showed that the basis of the physiological rest of oocytes is the suppression of the activity of mitochondria, namely complex I of the respiratory chain. Due to this, the amount of reactive oxygen species (ROS) in resting oocytes is significantly reduced.

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The follicle of the human ovary. Red shows the activity of ROS. A drawing from an article in Nature.

Scientists began by using special dyes to assess the level of ROS in early human oocytes and the frog Xenopus laevis. In both cases, the amount of ROS was insignificant, although they were detected in the surrounding cells. Attempts to cause oxidative stress in oocytes using the agent menadion, stimulating the formation of ROS, led to the fact that about 80% of the early frog oocytes died.

Next, the researchers studied in detail the functioning of mitochondria in human and frog oocytes. It turned out that, in comparison with the surrounding cells, the mitochondria of oocytes have a lower membrane potential and, in general, a lower level of respiratory activity. The authors showed that inhibition of the II, III, IV and V complexes of the mitochondrial respiratory chain was detrimental to frog oocytes. Insensitivity to inhibitors of complex I suggests that it is not the only necessary way for electrons to enter the respiratory chain in the mitochondria of oocytes.

The authors also studied the mitochondrial proteome of oocytes. It turned out that in early oocytes, the most numerous proteins are mitochondrial proteases and chaperones, which are usually activated in response to the appearance of a large number of incorrectly stacked proteins in mitochondria. In general, the number of subunits of respiratory chain complexes in them was reduced, and this effect was especially pronounced in the case of complex I.

Thus, in early oocytes, complex I in mitochondria is not necessary for survival. The authors showed that the level of ROS in oocytes is lower precisely due to a decrease in the number of complex I molecules, one of their main generators in mitochondria. The researchers note that at the moment, early vertebrate oocytes are the first known cells that can exist without the functional complex I of the mitochondrial respiratory chain.

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