SLC25A5

Description

The SLC25A5 (solute carrier family 25 member 5) is a protein-coding gene located on chromosome X.

ADP/ATP translocase 2 is a protein that in humans is encoded by the SLC25A5 gene on the X chromosome. This protein functions as an antiporter for ADP/ATP exchange between the mitochondrial matrix and cytoplasm. As a result, it plays a key role in maintaining mitochondrial membrane potential and inhibiting apoptosis and has been targeted for treating cancer.

== Structure == The SLC25A5 gene belongs to the ANT gene family, which itself belongs to the superfamily that includes genes encoding brown fat mitochondrial uncoupling proteins and mitochondrial phosphate carrier proteins. Compared to the other gene isoforms, SLC25A5 possesses different motifs, including a CCACT sequence rather than the canonical CCAAT sequence upstream of the TATA box, as well as five SP1 binding sites. This gene consists of 4 exons, while its encoded protein forms a homodimer embedded in the inner mitochondrial membrane. The entire protein is composed of 300-320 amino acid residues folded into six transmembrane helices. The human genome contains four differentially expressed isoforms, as well as several non-transcribed pseudogenes, of this gene.

== Function == This gene is a member of the mitochondrial carrier subfamily of solute carrier protein genes. The product of this gene, adenine nucleotide translocator 2 (ANT2), functions as a major constituent of the mitochondrial permeability-transition pore complex that catalyzes the exchange of mitochondrial ATP with cytosolic ADP. As a result of its antiporter function, ANT2 maintains mitochondrial membrane potential by regulating ADP/ATP ratios in oxidative phosphorylation.

SLC25A5, also known as ADP/ATP translocase 2 (ANT2), is an ADP:ATP antiporter that facilitates the import of ADP into the mitochondrial matrix for ATP synthesis and the export of ATP to fuel cellular processes. It operates through an alternating access mechanism, transitioning between a cytoplasmic-open state (c-state) and a matrix-open state (m-state). This dynamic process involves a single substrate-binding site that is alternately exposed to either the cytosolic or matrix side of the inner mitochondrial membrane. Beyond its primary role in ADP:ATP exchange, SLC25A5 is also implicated in mitochondrial uncoupling and the regulation of the mitochondrial permeability transition pore (mPTP). It acts as a proton transporter, contributing to mitochondrial thermogenesis by uncoupling proton flow through the electron transport chain and ATP synthase. However, this proton transporter activity is inhibited by its ADP:ATP antiporter function, suggesting a delicate balance between ATP production and thermogenesis. Interestingly, SLC25A5 requires free fatty acids as a cofactor for proton transport but does not transport these fatty acids itself. It is believed to mediate mitochondrial uncoupling in tissues lacking UCP1. SLC25A5 plays a crucial role in the opening of the mPTP, a non-specific pore that allows the passage of solutes up to 1.5 kDa across the mitochondrial membranes, potentially contributing to cell death. While the exact mechanism is not fully understood, it remains unclear whether SLC25A5 forms part of the mPTP structure or simply regulates its activity. Independently of its ADP:ATP antiporter function, SLC25A5 acts as a regulator of mitophagy, a process that removes damaged mitochondria. It interacts with TIMM44, leading to the inhibition of TIMM23, a component of the presequence translocase, and ultimately promoting the stabilization of PINK1, a key regulator of mitophagy. Furthermore, as a component of the MMXD complex, which is associated with the mitotic spindle, SLC25A5 may contribute to chromosome segregation.

SLC25A5 is also known as 2F1, AAC2, ANT2, T2, T3.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing