Mitophagy and spermatogenesis: Role and mechanisms

Abstract

The mitophagy process, a type of macroautophagy, is the targeted removal of mitochondria. It is a type of autophagy exclusive to mitochondria, as the process removes defective mitochondria one by one. Mitophagy serves as an additional level of quality control by using autophagy to remove superfluous mitochondria or mitochondria that are irreparably damaged. During spermatogenesis, mitophagy can influence cell homeostasis and participates in a variety of membrane trafficking activities. Crucially, it has been demonstrated that defective mitophagy can impede spermatogenesis. Despite an increasing amount of evidence suggesting that mitophagy and mitochondrial dynamics preserve the fundamental level of cellular homeostasis, little is known about their role in developmentally controlled metabolic transitions and differentiation. It has been observed that male infertility is a result of mitophagy's impact on sperm motility. Furthermore, certain proteins related to autophagy have been shown to be present in mammalian spermatozoa. The mitochondria are the only organelle in sperm that can produce reactive oxygen species and finally provide energy for sperm movement. Furthermore, studies have shown that inhibited autophagy-infected spermatozoa had reduced motility and increased amounts of phosphorylated PINK1, TOM20, caspase 3/7, and AMPK. Therefore, in terms of reproductive physiology, mitophagy is the removal of mitochondria derived from sperm and the following preservation of mitochondria that are exclusively maternal.

Keywords: Autophagy; Male infertility; Reproductive health; Spermatogenesis.

Fig. 1

Diagram of candidate pathways leading to sperm mitophagy by autophagy and ubiquitin proteasome system. Autophagy begins with the aggregation and ubiquitination of proteins or organelles that require recycling. Multiubiquitin chains on these aggregates are recognized by ubiquitin-binding autophagy receptors and are brought to phagophore, a membranous organelle that eventually closes around the protein aggregate to form an autophagosome. Finally, autophagosome fuses with a lysosome that contains proteases able to degrade the protein cargo.