ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell (PubMed:31618756, PubMed:31341297). 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 (By similarity). In addition to its ADP:ATP antiporter activity, also involved in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity (PubMed:31489369, PubMed:31341297). 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 (PubMed:31341297). 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) (PubMed:31341297). Proton transporter activity requires free fatty acids as cofactor, but does not transport it (PubMed:31341297). Probably mediates mitochondrial uncoupling in tissues that do not express UCP1 (PubMed:31341297). 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 (PubMed:31489369). It is however unclear if SLC25A4/ANT1 constitutes a pore-forming component of mPTP or regulates it (PubMed:31489369). 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 (PubMed:31618756). ADP(in) + ATP(out) = ADP(out) + ATP(in) H(+)(in) = H(+)(out) The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA) (By similarity). The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR) (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity (PubMed:31341297). Monomer (By similarity). Found in a complex with ARL2, ARL2BP and SLC25A4/ANT1 (PubMed:11809823). Interacts with ARL2BP (PubMed:11809823). Interacts with TIMM44; leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1 (PubMed:31618756). The complex formed with ARL2BP, ARL2 and SLC25A4/ANT1 is expressed in mitochondria (PubMed:11809823). May localize to non-mitochondrial membranes (By similarity). Highly expressed in heart, skeletal muscle and brain. The transmembrane helices are not perpendicular to the plane of the membrane, but cross the membrane at an angle. Odd-numbered transmembrane helices exhibit a sharp kink, due to the presence of a conserved proline residue. Under cell death induction, transglutaminated by TGM2 (PubMed:19644512). Transglutamination leads to formation of covalent cross-links between a glutamine and the epsilon-amino group of a lysine residue, forming polymers (PubMed:19644512). Mice display mitochondrial myopathy affecting heart and skeletal muscles (PubMed:9207786). Hindlimb muscles exhibit abundant ragged-red fibers, characteristic of mitochondrial myopathies (PubMed:9207786). Increased mitochondrial activity is observed, reflecting greater mitochondrial content (PubMed:9207786). In addition, mice are exercise intolerant (PubMed:9207786). Mice develop chronic progressive external ophthalmoplegia, but show normal ocular motility (PubMed:16303948). In retina, while abnormalities are observed in extraocular muscles, retinal structure and function are not affected normal (PubMed:20671283). Cells display impaired mitochondrial uncoupling (PubMed:31341297). Cells show impaired autophagy, leading to accumulation of aberrant mitochondria (PubMed:31618756). Mice lacking Slc25a4/Ant1 and Slc25a5/Ant2 in liver still have mitochondrial permeability transition pore (mPTP) activity, although more Ca(2+) is required to activate the mPTP (PubMed:14749836). Deletion of Slc25a4/Ant1, Slc25a5/Ant2 and Slc25a31/Ant4 in liver completely inhibits mPTP (PubMed:31489369). Mice lacking Slc25a4/Ant1, Slc25a5/Ant2, Slc25a31/Ant4 and Ppif lack Ca(2+)-induced mPTP formation (PubMed:31489369). Belongs to the mitochondrial carrier (TC 2.A.29) family. Was reported as a homodimer (PubMed:11809823). However, 3D structure data show that it forms a monomer (By similarity). It is unclear if SLC25A4/ANT1 constitutes a pore-forming component of mitochondrial permeability transition pore (mPTP) (PubMed:14749836, PubMed:31489369). Initial reports, based on deletion of Slc25a4/Ant1 and Slc25a5/Ant2, suggested that ADP/ATP translocase rather acts as a regulator of mPTP (PubMed:14749836). However, deletion of all ADP/ATP translocase components (Slc25a4/Ant1, Slc25a5/Ant2 and Slc25a31/Ant4) completely inhibits mPTP, suggesting that ADP/ATP translocase constitutes a pore-forming component of mPTP (PubMed:31489369). Discrepancy between reports may be caused by overexpression of Slc25a31/Ant4 in mice lacking Slc25a4/Ant1 and Slc25a5/Ant2, which compensates for the loss of Slc25a4/Ant1 and Slc25a5/Ant2 (PubMed:31489369).