Slc25a33, a member of the solute carrier family 25, functions as a mitochondrial pyrimidine nucleotide transporter [2]. It plays a crucial role in importing/exporting pyrimidine nucleotides into and from mitochondria, which is essential for mitochondrial DNA and RNA synthesis and breakdown. This gene is also involved in pathways related to innate immunity and is potentially associated with mitochondrial function-related processes [1,3]. Genetic models can be valuable in studying its functions in vivo.

In terms of key findings, the mitochondrial protease YME1L proteolysis of SLC25A33 helps preserve pyrimidine pools. Deficiency of YME1L leads to SLC25A33-dependent release of mtDNA and a cGAS-STING-TBK1-dependent inflammatory response, which is induced by cellular pyrimidine deficiency [1]. In addition, in diabetic retinopathy rats, the expression of SLC25A33 is increased, suggesting its potential as a biomarker and therapeutic target for this disease [3].

In conclusion, Slc25a33 is essential for mitochondrial nucleotide transport and is involved in innate immune responses and mitochondrial function. Studies using models like YME1L-deficient and diabetic retinopathy rats have revealed its role in inflammation and diabetic retinopathy, providing insights into potential disease mechanisms and therapeutic strategies related to these conditions.

References:

1. Sprenger, Hans-Georg, MacVicar, Thomas, Bahat, Amir, Giavalisco, Patrick, Langer, Thomas. 2021. Cellular pyrimidine imbalance triggers mitochondrial DNA-dependent innate immunity. In Nature metabolism, 3, 636-650. doi:10.1038/s42255-021-00385-9. https://pubmed.ncbi.nlm.nih.gov/33903774/

2. Di Noia, Maria Antonietta, Todisco, Simona, Cirigliano, Angela, Iacobazzi, Vito, Palmieri, Ferdinando. 2014. The human SLC25A33 and SLC25A36 genes of solute carrier family 25 encode two mitochondrial pyrimidine nucleotide transporters. In The Journal of biological chemistry, 289, 33137-48. doi:10.1074/jbc.M114.610808. https://pubmed.ncbi.nlm.nih.gov/25320081/

3. Peng, Li, Ma, Wei, Xie, Qing, Chen, Baihua. 2021. Identification and validation of hub genes for diabetic retinopathy. In PeerJ, 9, e12126. doi:10.7717/peerj.12126. https://pubmed.ncbi.nlm.nih.gov/34603851/