Slc25a35 belongs to the SLC25 family of mitochondrial carrier proteins. It is involved in mitochondrial metabolism, with functions such as transporting molecules across the mitochondrial membrane. The associated pathways may include those related to fatty acid oxidation (FAO) and mitochondrial biogenesis, which are crucial for maintaining normal cellular energy metabolism and function [1,4,5].

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 the proliferation and metastasis of HCC cells 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 upregulate Slc25a35 [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 relative to the prognosis and changed the tumor microenvironment, as well as the MYC and p53 signaling pathways [3].

In conclusion, Slc25a35 plays essential roles in mitochondrial-related metabolic processes. Studies, especially those using in vivo models like the DEN-induced HCC mice model, have revealed its oncogenic role in HCC. Its associations with IPF and PDAC also suggest its potential importance in these disease areas, providing insights into disease mechanisms and potential therapeutic targets.