Slc25a35, a member of the SLC25 family of mitochondrial carrier proteins, is involved in mitochondrial metabolism. It plays a role in transporting molecules across the mitochondrial membrane, and its function may be related to pathways such as fatty acid oxidation (FAO) and mitochondrial biogenesis, which are crucial for maintaining normal cellular functions [4,1].

In hepatocellular carcinoma (HCC), Slc25a35 was found to enhance FAO and mitochondrial biogenesis. It reprogramed mitochondrial metabolism, increasing oxygen consumption rate and ATP production while decreasing ROS level. Mechanistically, it upregulated peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) through increasing acetyl-CoA-mediated acetylation of PGC-1α. Functionally, it promoted HCC cell proliferation and metastasis both in vitro and in vivo, as well as carcinogenesis in a DEN-induced HCC mice model. Additionally, decreased miR-663a in HCC cells was found to contribute to Slc25a35 upregulation [1].

In a multi-omics analysis related to idiopathic pulmonary fibrosis (IPF), Slc25a35 was among the mitochondria-related genes significantly associated with IPF [2]. In pancreatic ductal adenocarcinoma (PDAC), SLC25A35 was significantly related to the prognosis, potentially changing the tumor microenvironment and affecting the MYC and p53 signaling pathways [3].

In conclusion, Slc25a35 has important functions in mitochondrial metabolism-related processes. Its study, especially through in vivo models like the DEN-induced HCC mice model, reveals its oncogenic role in HCC. The associations found in IPF and PDAC also suggest its potential significance in these disease areas, highlighting its importance as a potential therapeutic target for related diseases.