Solute carrier family 25 member 47 (SLC25A47)

Solute carrier family 25 member 47 (SLC25A47) is a mitochondrial inner membrane transporter, highly and selectively expressed in liver hepatocytes. SLC25A47 is the only member of the SLC25A family with this liver specificity, where it functions as a pivotal regulator of gluconeogenesis, exporting key metabolites (such as malate) required for glucose production during fasting and maintaining overall energy homeostasis[1]. SLC25A47 acts as a mitochondrial NAD(+) transporter, supplying NAD(+) to SIRT3 and thus activating the downstream AMPKα signaling pathway, which in turn suppresses SREBP-driven lipid biosynthesis and promotes lipid homeostasis[4][6]. Genetic variants in SLC25A47 are associated with altered glucose and lipid metabolism in humans, linking it to diseases such as type 2 diabetes and NAFLD[1][2]. SLC25A47 functionality is also implicated in hepatocellular carcinoma progression as it is commonly downregulated in HCC[4]. Pharmacologically, SLC25A47 is activated by metformin, which enhances its expression and beneficially impacts hepatic AMPK signaling and metabolic control[2][4]. While SLC25A47 represents a promising therapeutic target for metabolic and liver diseases, loss of its function can lead to mitochondrial stress, lipid accumulation, fibrosis, and heightened cancer risk, highlighting the need for careful modulation in any drug development strategy[1][3].

Other names

C14orf68HDMCPHMFN1655HDCMPHepatocellular carcinoma down-regulated mitochondrial carrier proteinMitochondrial NAD(+) transporter SLC25A47HCC down-regulated mitochondrial carrier protein

Activation of SLC25A47 increases mitochondrial NAD(+), enhances SIRT3 deacetylase activity, which in turn activates AMPKα signaling and reduces hepatic lipid synthesis and gluconeogenesis. Metformin upregulates SLC25A47, leading to increased AMPKα phosphorylation and suppression of SREBP-mediated lipogenesis.