MORN4, a protein containing MORN (membrane occupation and recognition nexus) repeats, has diverse functions. It participates in protein-protein interactions and is involved in multiple biological pathways. In the context of heart-related functions, it has implications in mitochondrial dynamics and mitophagy, and in other aspects, it may be related to axonal degeneration and muscle-related processes [1,2,3].

In a mouse model of myocardial infarction (MI), knockdown of MORN4 accelerated cardiac injury, fibrosis, and deteriorated cardiac function, indicating its protective role against ischemic injury in cardiomyocytes. Mechanistically, MORN4 directly binds to MFN2 and promotes its phosphorylation through ROCK2, mediating beneficial mitophagy induced by mitochondrial dynamics. Sphingosylphosphorylcholine (SPC) alleviated ischemic cardiomyocyte apoptosis and heart injury by increasing MORN4 levels, highlighting the MORN4-MFN2 axis as a potential target for myocardial ischemia treatment [1]. In Drosophila, knockdown of retinophilin (rtp), the ortholog of MORN4, protected axons from taxol-induced degeneration, and MORN4 promoted axonal degeneration in mouse sensory axons following axotomy, suggesting its conserved role in promoting axonal degeneration [2].

In conclusion, MORN4 is crucial in maintaining myocardial mitochondrial homeostasis during ischemia and in the process of axonal degeneration. The findings from mouse and Drosophila models provide valuable insights into its functions, highlighting its potential as a therapeutic target for ischemic heart diseases and axonopathies.

References:

1. Zhou, Jinrun, Liu, Honghong, Zhang, Tianliang, Kong, Weihua, Zhao, Jing. 2023. MORN4 protects cardiomyocytes against ischemic injury via MFN2-mediated mitochondrial dynamics and mitophagy. In Free radical biology & medicine, 196, 156-170. doi:10.1016/j.freeradbiomed.2023.01.016. https://pubmed.ncbi.nlm.nih.gov/36682578/

2. Bhattacharya, Martha R C, Gerdts, Josiah, Naylor, Sarah A, Milbrandt, Jeffrey, DiAntonio, Aaron. . A model of toxic neuropathy in Drosophila reveals a role for MORN4 in promoting axonal degeneration. In The Journal of neuroscience : the official journal of the Society for Neuroscience, 32, 5054-61. doi:10.1523/JNEUROSCI.4951-11.2012. https://pubmed.ncbi.nlm.nih.gov/22496551/

3. Alsoufi, Mohammed Abdulwahid, Liu, Yong, Cao, Changwei, He, Yang, Ge, Changrong. 2022. Integrated Transcriptomics Profiling in Chahua and Digao Chickens' Breast for Assessment Molecular Mechanism of Meat Quality Traits. In Genes, 14, . doi:10.3390/genes14010095. https://pubmed.ncbi.nlm.nih.gov/36672833/