SLC25A4
SLC25A4 (solute carrier family 25 member 4), also known as ADP/ATP translocase 1, ANT1, AAC1 and adenine nucleotide translocator 1, is an inner mitochondrial membrane carrier. It exchanges ADP and ATP across the membrane and also contributes to mitochondrial uncoupling and permeability transition. Browse Assay Genie's current range of SLC25A4 research reagents below, or read on for the biology behind the target.
SLC25A4 is an ADP:ATP antiporter. It imports ADP into the mitochondrial matrix for ATP synthesis and exports ATP to fuel the cell. It works by an alternating access mechanism: a single substrate-binding site is exposed in turn to the cytosolic side (c-state) or the matrix side (m-state) of the inner mitochondrial membrane. Exchange is consecutive. One substrate is transported and dissociates before the second binds for transport in the opposite direction. NCBI describes the protein as a gated pore, and it forms a homodimer in the inner mitochondrial membrane.
Besides nucleotide exchange, SLC25A4 acts as a proton transporter that uncouples the proton flows of the electron transport chain and ATP synthase. This lowers the efficiency of ATP production and causes mitochondrial thermogenesis. The activity requires free fatty acids as a cofactor, which it does not transport, and it is inhibited by ADP:ATP antiporter activity. This suggests SLC25A4 (ANT1) is a master regulator of mitochondrial energy output, balancing ATP production against thermogenesis. It also plays a key role in opening of the mitochondrial permeability transition pore (mPTP), which contributes to cell death. It is unclear whether it forms the pore or regulates it. Independently of its antiporter activity, it promotes mitophagy by interacting with TIMM44, which inhibits the presequence translocase TIMM23 and stabilises PINK1.
The SLC25A4 gene belongs to the mitochondrial carrier subfamily of solute carrier genes (SLC25 group). Its earlier names include adenine nucleotide translocator 1, and the symbols PEO2 and PEO3 reflect progressive external ophthalmoplegia. Mutations in the gene have been shown to cause autosomal dominant progressive external ophthalmoplegia and familial hypertrophic cardiomyopathy. Mouse and rat both have an ortholog named Slc25a4.
SLC25A4 exchanges ADP and ATP across the inner membrane, making it central to studies of ATP supply from the mitochondrion to the cell.
As a fatty-acid-dependent proton transporter, SLC25A4 is studied for how mitochondria balance ATP production against heat generation.
SLC25A4 is involved in mPTP opening, which contributes to cell death, so it features in work on how this pore is regulated.
SLC25A4 promotes mitophagy via TIMM44 and PINK1 stabilisation, and its mutations are linked to progressive external ophthalmoplegia and hypertrophic cardiomyopathy.
SLC25A4 is an inner mitochondrial membrane antiporter that brings ADP into the matrix for ATP synthesis and exports ATP to the cytoplasm. It also acts as a proton transporter in mitochondrial uncoupling, takes part in mPTP activity, and regulates mitophagy independently of nucleotide exchange.
SLC25A4 is also called ADP/ATP translocase 1, adenine nucleotide translocator 1, ANT1, AAC1 and T1. The symbols PEO2 and PEO3 come from progressive external ophthalmoplegia, a disease linked to mutations in the gene. Its older HGNC name described it as a mitochondrial carrier, adenine nucleotide translocator, member 4.
Mouse and rat each have an ortholog called Slc25a4. In humans, mutations in SLC25A4 have been shown to cause autosomal dominant progressive external ophthalmoplegia and familial hypertrophic cardiomyopathy. Check the datasheet of any product for its validated reactivity.
Other solute carriers, mitochondrial import components and mitophagy regulators connected to SLC25A4 biology.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P12235; product specifications from Assay Genie datasheets.