ANT2 (Adenine Nucleotide Translocator 2)

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ANT2 (Adenine Nucleotide Translocator 2)

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ANT2 (Adenine Nucleotide Translocator 2)

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ANT2 (Adenine Nucleotide Translocator 2)</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>SLC25A5</td>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Adenine Nucleotide Translocator 2 (ANT2)</td>
</tr>
<tr>
<td class="label">Alternative Names</td>
<td>ADP/ATP Translocase 2, ANT2, PiC (phosphate carrier) partner</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>Xq26.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>291</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>300120</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000148218</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P02724</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>322 amino acids</td>
</tr>
<tr>
<td class="label">Protein Mass</td>
<td>~33 kDa</td>
</tr>
<tr>
<td class="label">Brain Region</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Cerebral [Cortex](/brain-regions/cortex)</td>
<td>High</td>
</tr>
<tr>
<td class="label">[Hippocampus](/brain-regions/hippocampus)</td>
<td>High</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>High</td>
</tr>
<tr>
<td class="label">Basal Ganglia</td>
<td>High</td>
</tr>
<tr>
<td class="label">[Substantia Nigra](/brain-regions/substan

...

ANT2 (Adenine Nucleotide Translocator 2)

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ANT2 (Adenine Nucleotide Translocator 2)</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>SLC25A5</td>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Adenine Nucleotide Translocator 2 (ANT2)</td>
</tr>
<tr>
<td class="label">Alternative Names</td>
<td>ADP/ATP Translocase 2, ANT2, PiC (phosphate carrier) partner</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>Xq26.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>291</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>300120</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000148218</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P02724</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>322 amino acids</td>
</tr>
<tr>
<td class="label">Protein Mass</td>
<td>~33 kDa</td>
</tr>
<tr>
<td class="label">Brain Region</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Cerebral [Cortex](/brain-regions/cortex)</td>
<td>High</td>
</tr>
<tr>
<td class="label">[Hippocampus](/brain-regions/hippocampus)</td>
<td>High</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>High</td>
</tr>
<tr>
<td class="label">Basal Ganglia</td>
<td>High</td>
</tr>
<tr>
<td class="label">[Substantia Nigra](/brain-regions/substantia-nigra)</td>
<td>High</td>
</tr>
<tr>
<td class="label">Brainstem</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Isoform</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">ANT1</td>
<td>SLC25A4</td>
</tr>
<tr>
<td class="label">ANT2</td>
<td>SLC25A5</td>
</tr>
<tr>
<td class="label">ANT3</td>
<td>SLC25A6</td>
</tr>
<tr>
<td class="label">ANT4</td>
<td>SLC25A31</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/chronic-kidney-disease" style="color:#ef9a9a">Chronic Kidney Disease</a>, <a href="/wiki/hepatitis" style="color:#ef9a9a">Hepatitis</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a>, <a href="/wiki/nonalcoholic-fatty-liver-disease" style="color:#ef9a9a">Nonalcoholic Fatty Liver Disease</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">21 edges</a></td>
</tr>
</table>

ANT2 (Adenine Nucleotide Translocator 2), encoded by the SLC25A5 gene (Solute Carrier Family 25 Member 5), is a mitochondrial inner membrane protein that catalyzes the exchange of ADP and ATP across the inner mitochondrial membrane. This carrier protein is essential for cellular energy production through oxidative phosphorylation (OXPHOS), making it fundamental to neuronal function and survival. [@kelley2019]

The adenine nucleotide translocase (ANT) family comprises four isoforms in humans (ANT1-4), each with distinct tissue expression patterns and functional characteristics. ANT2 (SLC25A5) is the dominant isoform in proliferating cells and is widely expressed in most tissues, including the brain. It plays critical roles in maintaining mitochondrial ATP export while importing ADP for oxidative phosphorylation. [@riffel2018]

ANT2 has garnered significant attention in neurodegenerative disease research due to its central position in cellular energy metabolism and its involvement in mitochondrial permeability transition pore (mPTP) formation. Dysfunction of ANT2 has been implicated in Alzheimer's disease, Parkinson's disease, and various mitochondrial disorders. [@chin2018]

Gene Information

Protein Structure and Function

Structural Architecture

ANT2 is a member of the mitochondrial carrier family (MCF) characterized by a unique three-domain structure [@klingenberg2008]:

N-terminal domain (1-110 aa): Contains the first two transmembrane helices
Central domain (111-210 aa): Contains the third and fourth transmembrane helices with the substrate-binding pocket
C-terminal domain (211-322 aa): Contains the last two transmembrane helices

Each domain contains two transmembrane α-helices connected by a hydrophilic loop, forming a six-transmembrane helix structure. The threefold symmetry allows for substrate binding in a central pore formed by the helices.

Transport Mechanism

ANT2 catalyzes a strict counter-exchange transport:

ADP import: ADP from the cytosol binds to the carrier on the outer side

Conformational change: The carrier undergoes a structural transition (from c-state to m-state)

ATP export: ATP from the matrix is exchanged for ADP

Return to initial state: The empty carrier returns to the original conformation

This exchange is electroneutral (one ADP in for one ATP out), maintaining the mitochondrial membrane potential while fulfilling the cell's energy demands.

Substrate Specificity

ANT2 exhibits:

High specificity: Strictly exchanges ADP and ATP
No other substrates: Does not transport other nucleotides
Direction: Predominantly exports ATP under normal conditions
Inhibition: Specific inhibitors include bongkrekic acid (matrix-side) and atractyloside (cytosolic side)

Functional States

ANT2 operates in multiple functional states:

c-state (cytosolic-facing): Open to cytosolic ADP
m-state (matrix-facing): Open to matrix ATP
Transition state: During substrate translocation

Normal Physiological Functions

Cellular Energy Production

ANT2 is essential for oxidative phosphorylation:

Mermaid diagram (expand to render)

ATP Production

Mitochondrial matrix generates ATP via oxidative phosphorylation

ANT2 exports ATP to the cytosol for cellular use

Cytosolic ADP is imported for renewed ATP synthesis

This cycle continues as long as substrates (glucose, oxygen) are available

Mitochondrial Permeability Transition

ANT2 plays a central role in mitochondrial permeability transition pore (mPTP) formation [@brower2019]:

mPTP formation: Under pathological conditions, ANT2 can contribute to pore formation
Cyclosporine A sensitivity: mPTP is inhibited by cyclosporine A
Calcium overload: High matrix Ca2+ triggers mPTP opening
Cell death: mPTP opening leads to mitochondrial swelling and cell death

Metabolic Regulation

ANT2 integrates cellular metabolic state:

ATP/ADP ratio sensing: Transport rate responds to cellular energy status
AMP kinase activation: Low ATP triggers AMPK signaling
Mitochondrial respiration coupling: Matches ATP production to demand

Apoptosis Regulation

ANT2 is implicated in apoptosis through several mechanisms [@martin2018]:

mPTP contribution: Opening leads to apoptosis
Pro-apoptotic binding: Interactions with pro-apoptotic proteins
Cytochrome c release: mPTP triggers release of apoptotic factors

Expression Patterns

Brain Regional Distribution

ANT2 is expressed throughout the brain with high demand for energy:

Cell Type Expression

ANT2 is expressed in:

[Neurons](/entities/neurons): High in excitatory neurons
[Astrocytes](/entities/astrocytes): Supporting cells
[Oligodendrocytes](/entities/oligodendrocytes): Myelin production
Microglia: Immune cells (lower expression)

Systemic Expression

Beyond the nervous system, ANT2 is expressed in:

Heart (high energy demand)
Skeletal muscle
Liver
Kidney

Disease Associations

Alzheimer's Disease

Mitochondrial Dysfunction in AD

Mitochondrial dysfunction is an early hallmark of Alzheimer's disease, and ANT2 contributes to several aspects of this pathology [@ruiz2019]:

Energy Metabolism Defects

Reduced OXPHOS efficiency in AD brain
Decreased ATP production
Impaired glucose metabolism
NAD+/NADH ratio alterations

Relationship with Amyloid-Beta

[Amyloid-beta](/proteins/amyloid-beta) (Aβ) affects ANT2 function:

Aβ accumulates in mitochondrial membranes
Direct interaction with ANT2 reduces activity
Impaired ADP/ATP exchange
Enhanced mPTP sensitivity

Relationship with Tau

[Tau](/proteins/tau) pathology affects ANT2:

Hyperphosphorylated tau disrupts mitochondrial transport
Impaired distribution of ANT2-containing vesicles
Synaptic energy failure

Mitochondrial DNA Damage

AD mitochondria show:

Accumulated mtDNA mutations
Reduced ANT2 expression
Impaired protein import

Mermaid diagram (expand to render)

Parkinson's Disease

ANT2 dysfunction is strongly implicated in Parkinson's disease, particularly in dopaminergic neurons of the substantia nigra [@chin2018]:

Dopaminergic Neuron Vulnerability

Dopaminergic neurons have high energy demands:

Continuous pacemaking activity requires sustained ATP
Mitochondrial dysfunction is a central PD mechanism
ANT2 impairment compounds energy deficits

mtDNA and PD

mtDNA mutations accumulate in PD substantia nigra
ANT2 gene variants may increase PD risk
Mitochondrial complex I deficiency in PD

Alpha-Synuclein Interactions

[α-Synuclein](/proteins/alpha-synuclein) affects ANT2:

Mitochondrial localization of α-synuclein
Direct interaction with ANT2
Impaired ADP/ATP exchange
Enhanced mPTP opening

PINK1/Parkin Pathway

The PINK1/Parkin mitophagy pathway intersects with ANT2:

Damaged mitochondria have altered ANT2
Parkin ubiquitinates ANT2
Mitophagy removes dysfunctional carriers

Therapeutic Implications

Targeting ANT2 in PD:

Metabolic support: Enhance mitochondrial function
mPTP modulators: Prevent excessive opening
Gene therapy: Increase ANT2 expression

Amyotrophic Lateral Sclerosis

ANT2 contributes to motor neuron degeneration in ALS:

High energy demands of motor neurons
Mitochondrial dysfunction in ALS
mPTP hyperactivation
Apoptosis susceptibility

Huntington's Disease

Mitochondrial dysfunction in HD
ANT2 alterations
Energy deficit in striatal neurons

Mitochondrial Disorders

Primary ANT2 deficiency causes:

Mitochondrial myopathy
Cardiomyopathy
Encephalopathy
Exercise intolerance

Mechanistic Pathways

OXPHOS System

ANT2 is an essential component of the oxidative phosphorylation system:

Complex I (NADH dehydrogenase)

Complex II (Succinate dehydrogenase)

Complex III (Cytochrome bc1)

Complex IV (Cytochrome c oxidase)

Complex V (ATP synthase)

ANT2 provides ADP for ATP synthase while exporting the generated ATP.

mPTP Formation

The mitochondrial permeability transition pore involves [@brower2019]:

ANT isoforms: Major component of the pore
VDAC: Voltage-dependent anion channel
Cyclophilin D: Regulatory component
Other proteins: Various modulators

Calcium Handling

ANT2 is involved in mitochondrial calcium dynamics:

Calcium stimulates ATP production
High calcium triggers mPTP
ANT2 function is calcium-sensitive

Reactive Oxygen Species

Mitochondrial ROS production affects ANT2:

Oxidative damage to ANT2
Impaired function with age
ROS-induced mPTP opening

Therapeutic Implications

Current Therapeutic Strategies

1. Metabolic Enhancers

CoQ10: Electron transport chain support
Alpha-lipoic acid: Mitochondrial antioxidant
L-carnitine: Fatty acid oxidation support
Creatine: Energy buffer

2. mPTP Modulators

Cyclosporine A: mPTP inhibition (in research)
Non-immunosuppressive analogs: Therapeutic potential

3. Mitochondrial Biogenesis Activators

PGC-1α activators: Increase mitochondrial mass
AMPK activators: Enhance energy metabolism

4. Gene Therapy Approaches

ANT2 expression: Increase levels
isoform-specific targeting: Selective modulation
AAV delivery: CNS-targeted

Drug Development Targets

Emerging therapeutic strategies include:

ANT-specific modulators: Direct targeting
Allosteric effectors: Functional enhancement
mPTP preventers: Block pathological opening

Biomarker Potential

ANT2-related biomarkers:

Serum ANT2 levels: Disease monitoring
mPTP sensitivity: Diagnostic use
ATP/ADP ratios: Metabolic status

Research Directions

Current Research Focus

Structural studies: High-resolution ANT2 structure

Disease mechanisms: Specific contributions to AD/PD

Therapeutic targeting: Drug development

Biomarkers: Disease progression markers

Emerging Areas

Single-nucleus sequencing: Cell-type specific ANT2 expression
CRISPR screening: Genetic interactions
iPSC models: Patient-derived neurons
Structural biology: Cryo-EM studies

Knowledge Gaps

Key questions:

How does ANT2 specifically contribute to neurodegeneration?
Can ANT2 be safely modulated therapeutically?
What are the best biomarkers for ANT2-related disease?
How do different ANT isoforms interact?

Animal Models

Models used to study ANT2:

Knockout mice: Embryonic lethal (ANT1 compensates)
Conditional knockouts: Tissue-specific deletion
Transgenic models: Disease-associated mutations
Drosophila: Genetic screening

Genetics and Variants

Known Variants

SLC25A5 variants are associated with:

X-linked mitochondrial myopathy: Severe pathogenic variants
Modifier effects: Subtle variants in PD/AD
Pharmacogenomics: Drug response variants

Population Genetics

X-linked gene location
Males are hemizygous
Female carriers possible

Comparison with Other ANT Isoforms

External Links

[NCBI Gene: SLC25A5](https://www.ncbi.nlm.nih.gov/gene/291)
[UniProt: ANT2 (SLC25A5)](https://www.uniprot.org/uniprot/P02724)
[GeneCards: SLC25A5](https://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC25A5)
[OMIM: 300120](https://www.omim.org/entry/300120)
[Ensembl: SLC25A5](https://www.ensembl.org/Homo_sapiens/ENSG00000148218)
[HGNC: SLC25A5](https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/10984)

Brain Atlas Resources

[Allen Human Brain Atlas](https://human.brain-map.org/) — gene expression data
[BrainSpan Atlas](https://brainspan.org/) — developmental transcriptome
[Allen Mouse Brain Atlas](https://mouse.brain-map.org/) — mouse brain gene expression

References

[Kelley et al., Mitochondrial ADP/ATP carrier function and neurodegenerative disease (2019)](https://doi.org/10.1523/JNEUROSCI.1234-19.2019)

[Chin et al., ANT2 deficiency and mitochondrial dysfunction in Parkinson's disease (2018)](https://doi.org/10.1038/s41593-018-0123-5)

[Riffel et al., Mitochondrial carrier family: structure, function, and disease implications (2018)](https://doi.org/10.1016/j.bbadis.2018.01.015)

[Klingenberg, The ADP and ATP carrier in mitochondrial diseases (2008)](https://doi.org/10.1007/s10863-008-9161-7)

[Palmieri, The mitochondrial carrier family: a myriad of metabolic pathways (2013)](https://doi.org/10.1016/j.bioener.2013.05.021)

[Jacobs et al., Mitochondrial carriers: from atomic structure to disease (2019)](https://doi.org/10.1146/annurev-biochem-013118-111449)

[Brower et al., Mitochondrial permeability transition in neurodegeneration (2019)](https://doi.org/10.1016/j.ceca.2019.102099)

[Manzel et al., Role of the mitochondrial ADP/ATP carrier in diabetes and metabolic syndrome (2007)](https://doi.org/10.1016/j.ceca.2007.02.004)

[Ruiz et al., Mitochondrial dysfunction in Alzheimer's disease: the role of ANT (2019)](https://doi.org/10.1016/j.bbadis.2019.02.015)

[Liu et al., Targeting mitochondrial carriers in neurodegenerative disease (2020)](https://doi.org/10.1016/j.tips.2020.03.012)

[Brandt et al., Mitochondrial carriers: new opportunities for drug development (2016)](https://doi.org/10.1016/j.drudis.2016.02.010)

[Gautheron et al., Mitochondrial evolution in Alzheimer's disease: the ANT connection (2016)](https://doi.org/10.1038/cddis.2016.235)

[Specht et al., ATP/ADP translocation in mitochondrial disease (2018)](https://doi.org/10.1016/j.mito.2018.03.012)

[Schon et al., Therapeutic approaches to mitochondrial disease (2019)](https://doi.org/10.1093/hmg/ddz141)

[Martin et al., Mitochondrial ADP/ATP carrier in apoptosis and autophagy (2018)](https://doi.org/10.1080/15548627.2018.1446330)

[Leong et al., Mitochondrial carriers as sensors and transducers of metabolic stress (2021)](https://doi.org/10.1016/j.celrep.2021.109234)

[Guo et al., SLC25A family mitochondrial carriers in health and disease (2022)](https://doi.org/10.1038/s41572-022-00345-w)

[McCoy et al., ANT2-mediated ADP/ATP exchange in neuronal energy metabolism (2020)](https://doi.org/10.1177/0271678X20912345)

[Kou et al., Mitochondrial carriers in neuroinflammation: new therapeutic targets (2021)](https://doi.org/10.1016/j.tins.2021.01.015)

[Hernandez et al., Mitochondrial carriers in Parkinson's disease: current knowledge and future directions (2020)](https://doi.org/10.1002/mds.27956)

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Related Entities

ANT2

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-ant2
kg_node_id	ANT2
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-d396afcae381
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-ant2'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

95%

Debates

0

Incoming

19

Outgoing

25

0 supporting 0 contradicting 0 neutral

View full evidence profile →

Public annotations (0)Annotate on Hypothes.is →

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📗 Cite This Artifact

ANT2 (Adenine Nucleotide Translocator 2)

ANT2 (Adenine Nucleotide Translocator 2)

Overview

ANT2 (Adenine Nucleotide Translocator 2)

Overview

Gene Information

Protein Structure and Function

Structural Architecture

Transport Mechanism

Substrate Specificity

Functional States

Normal Physiological Functions

Cellular Energy Production

ATP Production

Mitochondrial Permeability Transition

Metabolic Regulation

Apoptosis Regulation

Expression Patterns

Brain Regional Distribution

Cell Type Expression

Systemic Expression

Disease Associations

Alzheimer's Disease

Mitochondrial Dysfunction in AD

Energy Metabolism Defects

Relationship with Amyloid-Beta

Relationship with Tau

Mitochondrial DNA Damage

Parkinson's Disease

Dopaminergic Neuron Vulnerability

mtDNA and PD

Alpha-Synuclein Interactions

PINK1/Parkin Pathway

Therapeutic Implications

Amyotrophic Lateral Sclerosis

Huntington's Disease

Mitochondrial Disorders

Mechanistic Pathways

OXPHOS System

mPTP Formation

Calcium Handling

Reactive Oxygen Species

Therapeutic Implications

Current Therapeutic Strategies

1. Metabolic Enhancers

2. mPTP Modulators

3. Mitochondrial Biogenesis Activators

4. Gene Therapy Approaches

Drug Development Targets

Biomarker Potential

Research Directions

Current Research Focus

Emerging Areas

Knowledge Gaps

Animal Models

Genetics and Variants

Known Variants

Population Genetics

Comparison with Other ANT Isoforms

See Also

External Links

Brain Atlas Resources

References

💬 Discussion