Artem Khan

An orphan no more: SLC25A45 controls mitochondrial import of methylated amino acids Solute carrier (SLC) genes encode the largest membrane transporter superfamily, with many orphan members of unknown function. In recent Cell Metabolism and Molecular Cell articles, Khan et al. and Dia...

Also thanks to Zachary Sebo and Navdeep Chandel for writing a preview to our work as well as a complementary study from Thomas MacVicar's lab www.cell.com/molecular-ce...

Machine-learning-guided discovery of SLC25A45 as a mediator of mitochondrial methylated amino acid import and carnitine synthesis Khan et al. apply machine learning to identify substrates of UNC93A, SLC45A4, and SLC25A45. Biochemical assays and in vivo metabolite tracing establish SLC25A45 as a key mediator of mitochondrial impo...

The link to our paper: dlvr.it/TP5gK5

The cover depicts a GWAS Manhattan plot as a city skyline reflected onto a New York City-style subway metabolic map: organelles as boroughs, metabolites as stations, transporters as trains.

Happy to see our recent work on SLC25A45 featured on the cover of @cp-cellmetabolism.bsky.social . Huge thanks to @yuyangliu.bsky.social for the design! @KivancBirsoy @rockefeller.edu

Thank you so much! I really appreciate your and Kevin's help!!

I would like to thank KivancBirsoy
for the mentorship as well as all the authors who made this work possible FrederickYen
@nicoledelgaudio.bsky.social
@gokhanunlu8.bsky.social
RanyaErdal MichaelXiao
KhandoWangdu KevinCho EricGamazon
@gjpattij.bsky.social

I also would like highlight two recent works on SLC45A4 nature.com/articles/s41... www.embopress.org/doi/full/10.... as well as a complementary work on SLC25A45 www.cell.com/molecular-ce...

Biochemically, SLC25A45 is necessary for the transport of methylated basic amino acids, such as trimethyllysine, and also ADMA.

We then showed that knockout of Slc25a45 in mice leads to an impaired carnitine biosynthesis which becomes limiting under fasting conditions, compromising β-oxidation and energy homeostasis.

We found SLC25A45 was significantly associated with trimethyllysine, a byproduct of protein catabolism and a precursor for carnitine biosynthesis.

Here, we used a machine-learning-guided approach to uncover the function of three transporters: UNC93A and SLC45A4 as mediators of plasma membrane acetyglucosamine and polyamines transport, respectively, and SLC25A45 as a mediator of mitochondrial methylated amino acid import.

Metabolic gene function discovery platform GeneMAP identifies SLC25A48 as necessary for mitochondrial choline import - Nature Genetics This study presents a multiomic Gene–Metabolite Association Prediction (GeneMAP) platform for discovery of metabolic gene function and identifies SLC25A48 as a mediator of mitochondrial choline import.

We previously developed GeneMAP, a metabolic gene discovery platform, to identify SLC25A48 as necessary for mitochondrial choline transporter. www.nature.com/articles/s41...

Solute carriers: The gatekeepers of metabolism Khan et al. outline key challenges in studying solute carrier (SLC) proteins, critical gatekeepers of metabolism, and propose directions for understanding their functions in physiology and disease.

Solute carriers are critical gatekeepers of metabolism; however, we don’t know the function of many of them as we emphasized in our recent perspective.
www.cell.com/cell/fulltex...

Machine-learning-guided discovery of SLC25A45 as a mediator of mitochondrial methylated amino acid import and carnitine synthesis Khan et al. apply machine learning to identify substrates of UNC93A, SLC45A4, and SLC25A45. Biochemical assays and in vivo metabolite tracing establish SLC25A45 as a key mediator of mitochondrial impo...

Excited to share our work on discovery of SLC25A45 as a mediator of mitochondrial methylated amino acid import and carnitine biosynthesis. @cp-cellmetabolism.bsky.social www.cell.com/cell-metabol...

SLC25A45 is required for mitochondrial uptake of methylated amino acids and de novo carnitine biosynthesis Dias et al. discover that the orphan solute carrier protein, SLC25A45, enables mitochondrial import of methylated amino acids. SLC25A45-dependent mitochondrial uptake of trimethyllysine drives carnitine biosynthesis. Mutation near its C terminus impacts SLC25A45 proteostasis and associates with altered methylated amino acid levels in human plasma.

Online Now: SLC25A45 is required for mitochondrial uptake of methylated amino acids and de novo carnitine biosynthesis Online now:

Machine-learning-guided discovery of SLC25A45 as a mediator of mitochondrial methylated amino acid import and carnitine synthesis Khan et al. apply machine learning to identify substrates of UNC93A, SLC45A4, and SLC25A45. Biochemical assays and in vivo metabolite tracing establish SLC25A45 as a key mediator of mitochondrial import of methylated amino acids and carnitine synthesis. Loss of Slc25a45 impairs fasting response by limiting carnitine availability for β-oxidation.

Online now: Machine-learning-guided discovery of SLC25A45 as a mediator of mitochondrial methylated amino acid import and carnitine synthesis

Solute carriers: The gatekeepers of metabolism Solute carrier (SLC) proteins play critical roles in maintaining cellular and organismal homeostasis by transporting small molecules and ions. Despite…

Excited to share our perspective on solute carrier transporters - gatekeepers of metabolism sciencedirect.com/science/arti... @KivancBirsoy
@YuyangLiu
@markgad.com
@TimCKenny
@cellpress.bsky.social
@rockefelleruniv.bsky.social