SLC25A5 Membrane Protein Introduction

Introduction of SLC25A5

SLC25A5 is encoded by SLC25A5 gene which is located on Xq24-q26. And the molecular mass of SLC25A5 is about 32 kDa. It mainly expressed in proliferative and undifferentiated cells. SLC25A5 belongs to the mitochondrial carrier (TC 2.A.29) family of which members are thought to have six transmembrane α-helical spanners and take part in transporting nucleotides, amino acids, inorganic ions and co-factors, keto acids, across the mitochondrial inner membrane.

Basic Information of SLC25A5
Protein Name ADP/ATP translocase 2
Gene Name SLC25A5
Aliases ADP,ATP carrier protein 2, ADP,ATP carrier protein, fibroblast isoform, Adenine nucleotide translocator 2, ANT 2, Solute carrier family 25 member 5
Organism Homo sapiens (Human)
UniProt ID P05141
Transmembrane Times Multi-pass membrane
Length (aa) 298

Function of SLC25A5 Membrane Protein

SLC25A5 mainly acts as an antiporter for ADP/ATP, facilitating the exchange of cytoplasmic ADP with mitochondrial ATP across the mitochondrial inner membrane. Expression of SLC25A5 is activated during cell proliferation and is repressed when cells become growth arrested. Accordingly, SLC25A5 also participates in the formation of the mitotic spindle-associated MMXD complex, so it may function in chromosome segregation. Besides, SLC25A5 is related to adenine transmembrane transporter activity, RNA binding and ubiquitin protein ligase binding. What’ s more, the expression of SLC25A5 is an important index of carcinogenesis because it is related to the rate of glycolytic metabolism. Compared with F1F0-ATPase, SLC25A5 has the opposite effect in the mitochondrial matrix, but their functions together maintain the mitochondrial membrane potential and ensure cell survival and proliferation. Beyond that, SLC25A5 can regulate the selective elimination of senescent cells targeted by mitochondrial. It has been shown that SLC25A5 directly bound to sesaminol, which pleiotropically upregulate cyclin D1 expression with protein stabilization and mTORC1 activation.

Role of ANT isoforms (including SLC25A5) in oxidative phosphorylation and glycolysis Fig.1 Role of ANT isoforms (including SLC25A5) in oxidative phosphorylation and glycolysis (Chevrollier, 2011).

Application of SLC25A5 Membrane Protein in Literature

  1. Hubackova S., et al. Selective elimination of senescent cells by mitochondrial targeting is regulated by ANT2. Cell Death & Differentiation. 2018. PubMed ID: 29786070

    This article focuses on cellular senescence, a kind of cycle arrest. Authors find that ANT2, also named SLC25A5, is related to the selective elimination of senescent cells targeted by mitochondrial, downregulation of SLC25A5 in nonsenescent cells promoted their MitoTam-triggered elimination, while restoration has the opposite effect.

  2. Baik S.H., et al. ANT2 shRNA downregulates miR-19a and miR-96 through the PI3K/Akt pathway and suppresses tumor growth in hepatocellular carcinoma cells. Experimental & Molecular Medicine. 2016, 48(3): e222. PubMed ID: 27012708

    MicroRNA is abnormal in many cancers, authors of this article study the function of SLC25A5 shRNA-regulated miRNAs in the pathogenesis of HCC. SLC25A5 can regulate the expression of miR-19a and miR-96, which leads to the suppression of tumor growth.

  3. Watanabe M., et al. The pleiotropic regulation of cyclin D1 by newly identified sesaminol-binding protein ANT2. Oncogenesis. 2017, 6(4): e311. PubMed ID: 28368390

    This article reveals that SLC25A5 binds to sesaminol, which may pleiotropically upregulate cyclin D1 expression at the mRNA level and protein level with mammalian target of rapamycin complex 1 (mTORC1) activation and protein stabilization.

  4. Jang J.Y., et al. Targeting adenine nucleotide translocase-2 (ANT2) to overcome resistance to epidermal growth factor receptor tyrosine kinase inhibitor in non-small cell lung cancer. Molecular Cancer Therapeutics. 2016, 15(6):1387. PubMed ID: 26883272

    Authors of this article want to study the therapeutic potential of ANT2, also named SLC25A5, inhibition to EGFR tyrosine kinase inhibitor (EGFR-TKI) resistance in non-small cell lung cancer. In the end, they find that the overexpression of SLC25A5 is related to the EGFR-TKI resistance, and SLC25A5 targeting may a novel strategy for solving this problem.

  5. Hubackova S., et al. IFNγ induces oxidative stress, DNA damage and tumor cell senescence via TGFβ/SMAD signaling-dependent induction of Nox4 and suppression of ANT2. Oncogene. 2015, 35(10):1236. PubMed ID: 25982278

    This article reveals differences between cytokine effects in mouse and human cells and mechanistically implicates the TGFβ/SMAD pathway, via induction of NADPH oxidases and suppression of ANT2, as key mediators of IFNγ/TNFα-evoked genotoxicity and cellular senescence.

SLC25A5 Preparation Options

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  1. Chevrollier A., et al. (2011). Adenine nucleotide translocase 2 is a key mitochondrial protein in cancer metabolism. Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1807(6), 562-567.

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