A Comprehensive Review of Mitochondrial Complex I During Mammalian Oocyte Maturation

Abstract

This review provides a comprehensive overview of Complex I during mammalian oocyte maturation. Complex I (NADH:ubiquinone oxidoreductase) is a crucial member of the electron transport chain and serves two principal functions during oxidative phosphorylation: NADH oxidation and proton pumping. It is located at the inner mitochondrial membrane and consists of 14 core and 31 accessory subunits that are necessary for its function and assembly. Moreover, Complex I is the primary site of reactive oxygen species (ROS) production among the different tissues. In light of the literature, it has been demonstrated that ROS and oxidative stress are significantly important among the various factors that can affect oocyte maturation. Factors such as malnutrition, alcohol use, obesity, PCOS, aging, and smoking are some of the common causes of infertility. Each one of them causes disruption in the equilibrium of the body's redox system and related with oxidative stress. During oocyte maturation, excessive ROS levels are associated with chromosomal errors and developmental insufficiency. In addition, excess oxidative stress adversely affects embryo growth and development and may cause fetal embryopathies with damage to macromolecules in the cytoskeleton. At this particular juncture, Complex I plays a key role in determining ROS production and the success of the oocyte maturation. This review evaluates mitochondrial Complex I's function, structure, and its crucial role during oocyte maturation.

Keywords: ROS; complex I; mitochondria; oocyte maturation; oogenesis; oxidative stress.

FIGURE 1

Schematic representation of (A) effect oxidative stress and (B) mammalian Complex I. (A) An imbalance in the redox system can lead to oxidative stress, potentially causing damage to DNA, RNA, and proteins. This may result in increased apoptosis and impaired embryonic development. (B) Mammalian Complex I is composed of N, Q, and P modules, each performing distinct functions. The N module is responsible for NADH oxidation, while the Q module mediates the conversion of ubiquinone to ubiquinol. The P module, comprising a proximal part (Pp) and a distal part (Pd), primarily functions in proton pumping. Core subunits of Complex I are indicated in bold, whereas accessory subunits are denoted in regular text. Proteins encoded by mitochondrial DNA are italicized, while those encoded by nuclear DNA are presented in standard formatting.

FIGURE 2

Schematic representation of (A) a positive feedback loop in Complex I dysfunction and (B) Complex I subunits during mammalian oogenesis. (A) For Complex I to work properly, the NADH/NAD⁺ ratio needs to stay low. If Complex I becomes less efficient at oxidizing NADH, it produces more reactive oxygen species (ROS). These ROS then further reduce Complex I's ability to oxidize NADH, creating a self‐perpetuating cycle. (B) Mitochondrial Complex I, a multi‐subunit enzyme serves a critical role in supporting mammalian oogenesis.

FIGURE 3

Representative figure illustrating Complex I expression levels during mammalian oocyte maturation, along with a schematic summary of related studies on Complex I and oocytes.