SLC25A5

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 mitochondrial matrix into the cytoplasm. The protein forms a homodimer embedded in the inner mitochondria membrane. Suppressed expression of this gene has been shown to induce apoptosis and inhibit tumor growth. The human genome contains several non-transcribed pseudogenes of this gene

Full Name

Solute Carrier Family 25 Member 51

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 (By similarity).
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 (By similarity).
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 (By similarity).
Proton transporter activity is inhibited by ADP:ATP antiporter activity, suggesting that SLC25A5/ANT2 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) (By similarity).
Proton transporter activity requires free fatty acids as cofactor, but does not transport it (By similarity).
Probably mediates mitochondrial uncoupling in tissues that do not express UCP1 (By similarity).
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:31883789).
It is however unclear if SLC25A5/ANT2 constitutes a pore-forming component of mPTP or regulates it (By similarity).
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 (By similarity).
As part of the mitotic spindle-associated MMXD complex it may play a role in chromosome segregation (PubMed:20797633).

Biological Process

Biological Process adaptive thermogenesisISS:UniProtKB
Biological Process adenine nucleotide transportManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process B cell differentiationISS:UniProtKB
Biological Process chromosome segregationIEA:UniProtKB-KW
Biological Process erythrocyte differentiationISS:UniProtKB
Biological Process mitochondrial ADP transmembrane transportISS:UniProtKB
Biological Process mitochondrial ATP transmembrane transportISS:UniProtKB
Biological Process negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of cell population proliferationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of mitophagyISS:UniProtKB
Biological Process regulation of mitochondrial membrane permeabilityISS:UniProtKB

Cellular Location

Mitochondrion inner membrane
Membrane
May localize to non-mitochondrial membranes.

Topology

Mitochondrial intermembrane: 1-7
Helical: 8-37
Mitochondrial matrix: 38-74
Helical: 75-99
Mitochondrial intermembrane: 100-109
Helical: 110-130
Mitochondrial matrix: 131-178
Helical: 179-199
Mitochondrial intermembrane: 200-210
Helical: 211-231
Mitochondrial matrix: 232-273
Helical: 274-291
Mitochondrial intermembrane: 292-298

PTM

Trimethylated by ANTKMT at Lys-52.