Slc25a48, a mitochondrial inner-membrane carrier protein, is crucial for mitochondrial choline transport. Choline is essential for phospholipid biosynthesis, neurotransmitter production, and one-carbon metabolism. Slc25a48-mediated choline import into mitochondria is part of these key metabolic pathways, and is important for maintaining normal cellular function [1].

In gene-knockout studies, loss of Slc25a48 impairs mitochondrial choline import. In cells lacking Slc25a48, there is increased production of mitochondrial reactive oxygen species, imbalanced mitochondrial lipids, decreased synthesis of purine nucleotides, and impaired cell proliferation [1,2]. Human cells with a single-nucleotide polymorphism on the Slc25a48 gene also show decreased mitochondrial choline import and increased oxidative stress [1].

In conclusion, Slc25a48 is a key regulator of mitochondrial choline catabolism, bioenergetics, and cell survival. The loss-of-function experiments, including gene-knockout models, have revealed its role in maintaining mitochondrial membrane integrity, supporting brown fat thermogenesis, and preventing oxidative stress-related cellular damage. Understanding Slc25a48 function may have implications for diseases related to choline metabolism, such as those associated with abnormal oxidative stress and cell proliferation [1].

References:

1. Verkerke, Anthony R P, Shi, Xu, Li, Mark, Gerszten, Robert E, Kajimura, Shingo. 2024. SLC25A48 controls mitochondrial choline import and metabolism. In Cell metabolism, 36, 2156-2166.e9. doi:10.1016/j.cmet.2024.07.010. https://pubmed.ncbi.nlm.nih.gov/39111307/

2. Verkerke, Anthony R P, Shi, Xu, Abe, Ichitaro, Gerszten, Robert E, Kajimura, Shingo. 2024. Mitochondrial choline import regulates purine nucleotide pools via SLC25A48. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.12.31.573776. https://pubmed.ncbi.nlm.nih.gov/38260464/