Fourteen novel human members of mitochondrial solute carrier family 25 (SLC25) widely expressed in the central nervous system

Haitina, Tatjana; Lindblom, Jessica; Renström, Thomas I.; Fredriksson, Robert

doi:10.1016/j.ygeno.2006.06.016

Cited by 155 publications

(147 citation statements)

References 42 publications

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“…2). Although SLC25A36 shares ϳ30% identity with SL25A32, SLC25A33 in turn is ϳ61% identical to SLC25A36 (21). SLC25A33 has previously been described as pyrimidine nucleotide carrier (PNC1) involved in mitochondrial pyrimidine nucleotide import (26), and for SLC25A36 a similar function has been suggested (22).…”

Section: Heterologous Expression Of Plant or Yeast Mitochondrial Nadmentioning

confidence: 98%

“…Similarly, in the yeast Saccharomyces cerevisiae, the proteins ScNDT1 and ScNDT2 constitute mitochondrial NAD ϩ transporters (20). In contrast to yeast and plants, no mitochondrial NAD ϩ transporter has been identified in humans or other mammals (12,21,22). On the other hand, a mammalian isoform of the essential NAD biosynthetic enzyme NMN adenylyl transferase (NMNAT), NMNAT3, has been shown to be targeted to the mitochondrial matrix when expressed from recombinant DNA.…”

Section: Endogenous Nmnat3 In the Mitochondria Of Human Cellsmentioning

confidence: 99%

“…For example, several homologs of the established plant and yeast NAD ϩ transporters exist in humans. SLC25A32, a member of the mitochondrial solute carrier family SLC25 (22) has recently been described as the mitochondrial folate carrier and is the closest homolog of AtNDT2 and ScNDT1, exhibiting 30 and 35% sequence identity with AtNDT2 and ScNDT1, respectively (12,21). Two more members of the SLC25 family, SLC25A33 and SLC25A36, display high sequence similarity with SLC25A32 (22).…”

Section: Endogenous Nmnat3 In the Mitochondria Of Human Cellsmentioning

confidence: 99%

“…Two more members of the SLC25 family, SLC25A33 and SLC25A36, display high sequence similarity with SLC25A32 (22). The strong conservation of the SLC25 proteins from yeast to humans and the fact that the predicted substrate binding sites were found almost identical still indicate that a mammalian mitochondrial transporter for a NAD-like substrate might exist (21). Furthermore, SLC25A32, SLC25A33, and SLC25A36 are the only mitochondrial carriers to share a peculiar feature (i.e.…”

Section: Endogenous Nmnat3 In the Mitochondria Of Human Cellsmentioning

confidence: 99%

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Subcellular Distribution of NAD+ between Cytosol and Mitochondria Determines the Metabolic Profile of Human Cells

VanLinden

Dölle

Pettersen

et al. 2015

Journal of Biological Chemistry

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Section: Heterologous Expression Of Plant or Yeast Mitochondrial Nadmentioning

confidence: 98%

Section: Endogenous Nmnat3 In the Mitochondria Of Human Cellsmentioning

confidence: 99%

Section: Endogenous Nmnat3 In the Mitochondria Of Human Cellsmentioning

confidence: 99%

Section: Endogenous Nmnat3 In the Mitochondria Of Human Cellsmentioning

confidence: 99%

See 2 more Smart Citations

Subcellular Distribution of NAD+ between Cytosol and Mitochondria Determines the Metabolic Profile of Human Cells

VanLinden

Dölle

Pettersen

et al. 2015

Journal of Biological Chemistry

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“…4 -8). The present investigation was undertaken to identify the function of SLC25A42, a novel member of the SLC25 family recently found in the human genome (9). SLC25A42 is 318 amino acids long and is highly expressed in virtually all tissues, in most at higher levels than many other SLC25 family members (9).…”

mentioning

confidence: 99%

A Novel Member of Solute Carrier Family 25 (SLC25A42) Is a Transporter of Coenzyme A and Adenosine 3′,5′-Diphosphate in Human Mitochondria

Fiermonte

Paradies

Todisco

et al. 2009

Journal of Biological Chemistry

138

139

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Mitochondrial carriers are a family of proteins that transport metabolites, nucleotides, and cofactors across the inner mitochondrial membrane thereby connecting cytosolic and matrix functions. The essential cofactor coenzyme A (CoA) is synthesized outside the mitochondrial matrix and therefore must be transported into mitochondria where it is required for a number of fundamental processes. In this work we have functionally identified and characterized SLC25A42, a novel human member of the mitochondrial carrier family. The SLC25A42 gene (Haitina, T., Lindblom, J., Renström, T., and Fredriksson, R., 2006, Genomics 88, 779 -790) was overexpressed in Escherichia coli, purified, and reconstituted into phospholipid vesicles. Its transport properties, kinetic parameters, and targeting to mitochondria demonstrate that SLC25A42 protein is a mitochondrial transporter for CoA and adenosine 3,5-diphosphate. SLC25A42 catalyzed only a counter-exchange transport, exhibited a high transport affinity for CoA, dephospho-CoA, ADP, and adenosine 3,5-diphosphate, was saturable and inhibited by bongkrekic acid and other inhibitors of mitochondrial carriers to various degrees. The main physiological role of SLC25A42 is to import CoA into mitochondria in exchange for intramitochondrial (deoxy)adenine nucleotides and adenosine 3,5-diphosphate. This is the first time that a mitochondrial carrier for CoA and adenosine 3,5-diphosphate has been characterized biochemically.The mitochondrial carrier family, or the solute carrier family 25 (SLC25), 3 comprises a large group of proteins that transport a variety of substrates across the inner mitochondrial membrane and, in a few cases, across other membranes (1, 2). Common structural features of the mitochondrial carrier family members consist in a tripartite structure (three repeats of ϳ100 amino acids), the presence of two transmembrane ␣-helices separated by hydrophilic loops in each repeat, and the presence of a signature motif at the C terminus of the first helix in each repeat (Ref. 3 and references therein). The SLC25 family is by far the largest of the currently known 43 SLC families. The Saccharomyces cerevisiae genome contains 35 members, that of Arabidopsis thaliana 58, and the human genome at least 48 SLC25 members. Until now, nearly 30 members and isoforms of this family have been identified in humans. These include the uncoupling protein and the carriers for ADP/ATP, phosphate, 2-oxoglutarate/malate, citrate, carnitine/acylcarnitine, dicarboxylates, ornithine and other basic amino acids, oxodicarboxylates, deoxynucleotides and thiamine pyrophosphate, aspartate-glutamate, glutamate, S-adenosylmethionine, ATPMg/Pi, pyrimidine nucleotides, and adenine nucleotides in peroxisomes (see Ref. 1 for a review and Refs. 4 -8). The present investigation was undertaken to identify the function of SLC25A42, a novel member of the SLC25 family recently found in the human genome (9). SLC25A42 is 318 amino acids long and is highly expressed in virtually all tissues, in most at higher levels than ma...

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UBE2A deficiency syndrome: Mild to severe intellectual disability accompanied by seizures, absent speech, urogenital, and skin anomalies in male patients

Leeuw

Bulk

Green

et al. 2010

American J of Med Genetics Pt A

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We describe three patients with a comparable deletion encompassing SLC25A43, SLC25A5, CXorf56, UBE2A, NKRF, and two non-coding RNA genes, U1 and LOC100303728. Moderate to severe intellectual disability (ID), psychomotor retardation, severely impaired/absent speech, seizures, and urogenital anomalies were present in all three patients. Facial dysmorphisms include ocular hypertelorism, synophrys, and a depressed nasal bridge. These clinical features overlap with those described in two patients from a family with a similar deletion at Xq24 that also includes UBE2A, and in several patients of Brazilian and Polish families with point mutations in UBE2A. Notably, all five patients with an Xq24 deletion have ventricular septal defects that are not present in patients with a point mutation, which might be attributed to the deletion of SLC25A5. Taken together, the UBE2A deficiency syndrome in male patients with a mutation in or a deletion of UBE2A is characterized by ID, absent speech, seizures, urogenital anomalies, frequently including a small penis, and skin abnormalities, which include generalized hirsutism, low posterior hairline, myxedematous appearance, widely spaced nipples, and hair whorls. Facial dysmorphisms include a wide face, a depressed nasal bridge, a large mouth with downturned corners, thin vermilion, and a short, broad neck.

show abstract

Fourteen novel human members of mitochondrial solute carrier family 25 (SLC25) widely expressed in the central nervous system

Cited by 155 publications

References 42 publications

Subcellular Distribution of NAD+ between Cytosol and Mitochondria Determines the Metabolic Profile of Human Cells

Subcellular Distribution of NAD+ between Cytosol and Mitochondria Determines the Metabolic Profile of Human Cells

A Novel Member of Solute Carrier Family 25 (SLC25A42) Is a Transporter of Coenzyme A and Adenosine 3′,5′-Diphosphate in Human Mitochondria

UBE2A deficiency syndrome: Mild to severe intellectual disability accompanied by seizures, absent speech, urogenital, and skin anomalies in male patients

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