UniprotKB/SwissProt ID: P48962 (P48962)
Gene Name:
Slc25a4
Organism: Mus musculus (Mouse)
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 (PubMed:31341297, PubMed:31618756). 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:31341297, PubMed:31489369). 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)
Other Modifications: View all modification sites in dbPTM
Protein Subcellular Localization: Mitochondrion inner membrane. Membrane
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