Slc25a10, also known as the dicarboxylate carrier (DIC), is a member of the mitochondrial carrier family. It is located in the mitochondrial inner membrane and is involved in transporting malate and succinate out of the mitochondria in exchange for phosphate and sulfate [9]. It has been suggested to participate in glutathione transport to mitochondria, which is crucial for reactive oxygen species scavenging and mitochondrial homeostasis [2,10]. It is also associated with pathways related to cell metabolism, redox-homeostasis, and apoptosis, and thus is of great biological importance. Genetic models, such as gene knockout models, can be valuable for studying its functions.

In osteosarcoma, knockdown of Slc25a10 suppressed cell proliferation, increased apoptosis, and decreased mitosis, indicating its oncogenic role, potentially mediated by CCNE1, P21, and P27 [1]. In H9c2 cardioblasts, inhibition of Slc25a10 aggravated ferroptosis, increased mitochondrial ROS, membrane depolarization, and GSH depletion [2]. In a patient with intractable epileptic encephalopathy and complex I deficiency, biallelic mutations in Slc25a10 led to reduction in RNA quantity, aberrant RNA splicing, absence of the protein and its transporting function, as well as defects in mitochondrial respiration and mitochondrial DNA content [3]. In myocardial ischemia/reperfusion injury, suppressing Slc25a10 partially reversed the protective effects of mild therapeutic hypothermia on cell injury, mitochondrial dysfunction, and the mitochondrial apoptosis pathway [4]. In colorectal cancer, Slc25a10 overexpression reversed the antitumor effects of PYCR1 silencing in vitro and inhibited the antitumor effects of erastin in vivo, indicating its role in promoting tumor growth and desensitizing cells to 5-FU cytotoxicity [5]. In A549 cells, knockdown of Slc25a10 changed the growth properties to a less malignant phenotype, increased glutamine dependency and sensitivity to oxidative stress, and caused an energy metabolic shift from glycolysis to mitochondrial oxidative phosphorylation [6]. In Hepa1-6 cells, knockout of Slc25a10 using Nuclease technology led to disordered glucose homeostasis, increased oxidative stress levels, and damaged electron transport chains [7]. In cancer cells, targeting Slc25a10 increased the cytotoxic effects of ionizing radiation and alleviated the improved antioxidant capacity and associated radioresistance induced by chronic-cycling hypoxia [8]. In lung cancer A549 cells, metformin treatment decreased the gene expression of Slc25a10, especially at low glucose concentrations [9]. In myocardial ferroptosis, absence of MPV17 led to ubiquitination-dependent degradation of Slc25a10, impairing mitochondrial glutathione import [10].

In conclusion, Slc25a10 is essential for maintaining mitochondrial function, cell metabolism, and redox-homeostasis. Through gene knockout or knockdown studies in various cell lines and in disease-related contexts such as cancer, cardiomyopathy, and neurodegenerative disorders, it has been shown to play significant roles in processes like cell proliferation, apoptosis, ferroptosis, and mitochondrial respiration. Understanding the functions of Slc25a10 can provide insights into the mechanisms of these diseases and potentially lead to new therapeutic strategies.