SLC25A4 Protein, Human (His)

SLC25A4 is an ADP:ATP antiporter that imports ADP into the mitochondrial matrix for ATP synthesis and exports ATP to fuel cellular processes. It cycles between cytoplasmic-open (c-state) and matrix-open (m-state) conformations via an alternating access mechanism, exposing a single substrate-binding site to either side of the inner mitochondrial membrane (By similarity). Beyond its ADP:ATP antiporter function, it participates in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity. As a proton transporter, it uncouples proton flow from the electron transport chain and ATP synthase, reducing ATP production efficiency and inducing mitochondrial thermogenesis (By similarity). This proton transport activity is inhibited by ADP:ATP antiporter activity, positioning SLC25A4/ANT1 as a master regulator balancing ATP synthesis and thermogenesis (By similarity). Proton transport requires free fatty acids as cofactors but does not translocate them (By similarity). It also plays a key role in mPTP opening, though its exact role (pore component vs. regulator) remains unclear (By similarity). Independently of its antiporter activity, it promotes mitophagy by binding TIMM44 to inhibit TIMM23, thereby stabilizing PINK1 (By similarity).