Recombinant Human ADP/ATP translocase 1 (SLC25A4), Truncated

Uniprot Id

P12235

Target Species

Human

Target Name

SLC25A4

Target Full Name

ADP/ATP translocase 1

Target Function

ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell. Cycles between the cytoplasmic-open state (c-state) and the matrix-open state (m-state): operates by the alternating access mechanism with a single substrate-binding site intermittently exposed to either the cytosolic (c-state) or matrix (m-state) side of the inner mitochondrial membrane. In addition to its ADP:ATP antiporter activity, also involved in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity. Plays a role in mitochondrial uncoupling by acting as a proton transporter: proton transport uncouples the proton flows via the electron transport chain and ATP synthase to reduce the efficiency of ATP production and cause mitochondrial thermogenesis. Proton transporter activity is inhibited by ADP:ATP antiporter activity, suggesting that SLC25A4/ANT1 acts as a master regulator of mitochondrial energy output by maintaining a delicate balance between ATP production (ADP:ATP antiporter activity) and thermogenesis (proton transporter activity). Proton transporter activity requires free fatty acids as cofactor, but does not transport it. Also plays a key role in mPTP opening, a non-specific pore that enables free passage of the mitochondrial membranes to solutes of up to 1.5 kDa, and which contributes to cell death. It is however unclear if SLC25A4/ANT1 constitutes a pore-forming component of mPTP or regulates it. Acts as a regulator of mitophagy independently of ADP:ATP antiporter activity: promotes mitophagy via interaction with TIMM44, leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1.

Target Involvement

Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 2 (PEOA2); Mitochondrial DNA depletion syndrome 12B, cardiomyopathic type (MTDPS12B); Mitochondrial DNA depletion syndrome 12A, cardiomyopathic type (MTDPS12A)

Target Subcellular Location

Mitochondrion inner membrane; Multi-pass membrane protein. Membrane; Multi-pass membrane protein.

Target Protein Families

Mitochondrial carrier (TC 2.A.29) family

Target Tissue Specificity

Expressed in erythrocytes (at protein level).

Target Research Area

Metabolism

Target Synonyms

SLC25A4; AAC1; ANT1; ADP/ATP translocase 1; ADP,ATP carrier protein 1; ADP,ATP carrier protein, heart/skeletal muscle isoform T1; Adenine nucleotide translocator 1; ANT 1; Solute carrier family 25 member 4

Target Background

This gene is a member of the mitochondrial carrier subfamily of solute carrier protein genes. The product of this gene functions as a gated pore that translocates ADP from the cytoplasm into the mitochondrial matrix and ATP from the mitochondrial matrix into the cytoplasm. The protein forms a homodimer embedded in the inner mitochondria membrane. Mutations in this gene have been shown to result in autosomal dominant progressive external opthalmoplegia and familial hypertrophic cardiomyopathy.