# MORN2 regulates the morphology and energy metabolism of mitochondria and is required for male fertility in mice

## TL;DR

MORN2 is crucial for male fertility in mice by regulating mitochondrial structure and function in sperm.

## Contribution

This study identifies MORN2 as a novel regulator of mitochondrial sheath formation and energy metabolism in sperm.

## Key findings

- Morn2–/– mice are infertile with sperm showing severe motility defects.
- MORN2 deficiency causes abnormal mitochondrial sheath formation and reduced respiratory activity in sperm.
- MORN2 is essential for maintaining mitochondrial membrane potential and reducing reactive oxygen species in sperm.

## Abstract

Mitochondria produce adenosine triphosphate through respiratory activities to power sperm differentiation and motility, and decreased mitochondrial respiratory activity can result in poor sperm motility and asthenospermia. The mitochondrial sheath is a component of the mid-piece of the sperm flagellum, and dysfunction of the sheath can reduce sperm motility and cause male infertility. The membrane occupation and recognition nexus-motif protein 2 (MORN2) is testis enriched in mice, and the MORN motif was reported to play a role in the regulation of bioelectrical signal homeostasis in cardiomyocytes.

We generated Morn2–/– mice using CRISPR/Cas9 and evaluated the potential functions of MORN2 in spermiogenesis through histological analysis, fertility examination, RT-PCR, CASA, immunofluorescence, TUNEL, electron microscopy analysis, mitochondrial energy metabolism analysis, etc.

The Morn2–/– mice were infertile, and their sperm showed severe motility defects. Morn2–/– sperm also had abnormal morphology characterized by bent heads, aberrant mitochondrial sheath formation, lower mitochondrial membrane potential, higher levels of reactive oxygen species, and decreased mitochondrial respiratory activity.

Our study demonstrates that MORN2 is essential for male fertility and indicates that MORN2 functions in mitochondrial sheath formation and regulates mitochondrial respiratory activity.

The online version contains supplementary material available at 10.1186/s12967-024-05010-3.