The mitochondrial carrier family was first characterized in the 1960s-1970s with the identification of specific transport systems for metabolites across the inner mitochondrial membrane. The malate carrier (then termed the dicarboxylate carrier or Pi-exchanger) was one of the first to be characterized biochemically. The molecular identification came later with the cloning and sequencing of SLC25A10 in the 1990s, which revealed homology to other mitochondrial carriers and established the now-extensive SLC25 gene family.
SLC25A10 encodes a mitochondrial carrier protein that transports malate and other dicarboxylates across the inner mitochondrial membrane. This protein plays a crucial role in the malate-aspartate shuttle, which transfers reducing equivalents across the mitochondrial membrane for oxidative phosphorylation. In neurons, proper function of this shuttle is essential for maintaining NADH/NAD+ ratios and supporting high energy demands of synaptic activity. Dysfunction has been implicated in various neurodegenerative diseases, including Alzheimer's and Parkinson's disease [1].
| Solute Carrier Family 25 Member 10 | |
|---|---|
| Gene Symbol | SLC25A10 |
| Full Name | Malate Carrier (dicarboxylate carrier) |
| Chromosome | 17q11.2 |
| NCBI Gene ID | [51175](https://www.ncbi.nlm.nih.gov/gene/51175) |
| OMIM | 609521 |
| Ensembl ID | ENSG00000183048 |
| UniProt ID | [Q9NS28](https://www.uniprot.org/uniprot/Q9NS28) |
| Associated Diseases | [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), Metabolic Disorders |
The SLC25 family (mitochondrial carrier proteins, MCPs) comprises over 50 members in humans, each transporting specific metabolites across the inner mitochondrial membrane. These carriers are essential for cellular metabolism, connecting cytosolic and mitochondrial pools of metabolites, nucleotides, and cofactors.
Key mitochondrial carriers include:
SLC25A10 is located on chromosome 17q11.2 and encodes a 303 amino acid protein. The protein adopts the typical mitochondrial carrier fold with six transmembrane alpha-helices and three internal repeat motifs. Each repeat contains a conserved sequence motif that forms the substrate binding site and translocation pathway.
SLC25A10 catalyzes the strict counterexchange of dicarboxylates:
The malate-aspartate shuttle is the primary means of transferring reducing equivalents (NADH) from the cytosol to the mitochondria in many tissues, including brain:
Cytosol:
OAA + NADH → Malate + NAD+ (MDH1)
↓ SLC25A10
Mitochondria:
Malate + NAD+ → OAA + NADH + H+ (MDH2)
↓ ETC
NADH → NAD+ + e- → ATP
This shuttle is essential for neuronal energy metabolism, particularly in regions with high oxidative phosphorylation demand.
SLC25A10 is expressed throughout the body with highest levels in tissues with high metabolic activity:
In brain, expression is high in neurons with high firing rates and synaptic activity.
Mitochondrial dysfunction is an early hallmark of AD:
In PD, mitochondrial dysfunction is well-established:
Strategies targeting mitochondrial carriers:
Agrimi G, et al. Mitochondrial carriers in neurodegeneration: a new therapeutic target. Journal of Neurochemistry. 2014. ↩︎
Rutherford CL, et al. Mitochondrial dysfunction in Alzheimer's disease. Nature Reviews Neuroscience. 2015. ↩︎
Monell A, et al. Mitochondrial carriers in Parkinson's disease. Movement Disorders. 2018. ↩︎