Mitochondrial Phosphate-carrier Deficiency: a Novel Disorder of Oxidative Phosphorylation

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2007 Feb 3

PMID 17273968

Citations 71

Authors

Johannes A Mayr

Olaf Merkel

Sepp D Kohlwein

Boris R Gebhardt

Hansjosef Bohles

Ulrike Fotschl

Johannes Koch

Michaela Jaksch

Hanns Lochmuller

Rita Horvath

Peter Freisinger

Wolfgang Sperl

Affiliations

Soon will be listed here.

Abstract

The mitochondrial phosphate carrier SLC25A3 transports inorganic phosphate into the mitochondrial matrix, which is essential for the aerobic synthesis of adenosine triphosphate (ATP). We identified a homozygous mutation--c.215G-->A (p.Gly72Glu)--in the alternatively spliced exon 3A of this enzyme in two siblings with lactic acidosis, hypertrophic cardiomyopathy, and muscular hypotonia who died within the 1st year of life. Functional investigation of intact mitochondria showed a deficiency of ATP synthesis in muscle but not in fibroblasts, which correlated with the tissue-specific expression of exon 3A in muscle versus exon 3B in fibroblasts. The enzyme defect was confirmed by complementation analysis in yeast. This is the first report of patients with mitochondrial phosphate-carrier deficiency.

Citing Articles

Electrophoresis-Correlative Ion Mobility Deepens Single-Cell Proteomics in Capillary Electrophoresis Mass Spectrometry.

Shen B, Zhou F, Nemes P Mol Cell Proteomics. 2024; 24(2):100892.

PMID: 39674510 PMC: 11875174. DOI: 10.1016/j.mcpro.2024.100892.

Comparative Genomics Provides Insights into Adaptive Evolution and Demographics of Bats.

Liu G, Pan Q, Zhu P, Guo X, Zhang Z, Li Z Mol Biol Evol. 2024; 41(12).

PMID: 39530650 PMC: 11646704. DOI: 10.1093/molbev/msae208.

Cancer Therapeutic Potential and Prognostic Value of the SLC25 Mitochondrial Carrier Family: A Review.

Gao R, Zhou D, Qiu X, Zhang J, Luo D, Yang X Cancer Control. 2024; 31:10732748241287905.

PMID: 39313442 PMC: 11439189. DOI: 10.1177/10732748241287905.

Slc25a3-dependent copper transport controls flickering-induced Opa1 processing for mitochondrial safeguard.

Murata D, Roy S, Lutsenko S, Iijima M, Sesaki H Dev Cell. 2024; 59(19):2578-2592.e7.

PMID: 38986607 PMC: 11461135. DOI: 10.1016/j.devcel.2024.06.008.

Hippocampal transcriptome-wide association study and pathway analysis of mitochondrial solute carriers in Alzheimer's disease.

Tian J, Jia K, Wang T, Guo L, Xuan Z, Michaelis E Transl Psychiatry. 2024; 14(1):250.

PMID: 38858380 PMC: 11164935. DOI: 10.1038/s41398-024-02958-0.

References

Kaukonen J, Juselius J, Tiranti V, Kyttala A, Zeviani M, Comi G . Role of adenine nucleotide translocator 1 in mtDNA maintenance. Science. 2000; 289(5480):782-5. DOI: 10.1126/science.289.5480.782. View

Haitina T, Lindblom J, Renstrom T, Fredriksson R . Fourteen novel human members of mitochondrial solute carrier family 25 (SLC25) widely expressed in the central nervous system. Genomics. 2006; 88(6):779-790. DOI: 10.1016/j.ygeno.2006.06.016. View

Skladal D, Halliday J, Thorburn D . Minimum birth prevalence of mitochondrial respiratory chain disorders in children. Brain. 2003; 126(Pt 8):1905-12. DOI: 10.1093/brain/awg170. View

Hamel P, Saint-Georges Y, de Pinto B, Lachacinski N, Altamura N, Dujardin G . Redundancy in the function of mitochondrial phosphate transport in Saccharomyces cerevisiae and Arabidopsis thaliana. Mol Microbiol. 2004; 51(2):307-17. DOI: 10.1046/j.1365-2958.2003.03810.x. View

Palmieri F . The mitochondrial transporter family (SLC25): physiological and pathological implications. Pflugers Arch. 2003; 447(5):689-709. DOI: 10.1007/s00424-003-1099-7. View

Mayr J, Paul J, Pecina P, Kurnik P, Forster H, Fotschl U . Reduced respiratory control with ADP and changed pattern of respiratory chain enzymes as a result of selective deficiency of the mitochondrial ATP synthase. Pediatr Res. 2004; 55(6):988-94. DOI: 10.1203/01.pdr.0000127016.67809.6b. View

Kiechl S, Horvath R, Luoma P, Kiechl-Kohlendorfer U, Wallacher-Scholz B, Stucka R . Two families with autosomal dominant progressive external ophthalmoplegia. J Neurol Neurosurg Psychiatry. 2004; 75(8):1125-8. PMC: 1739155. DOI: 10.1136/jnnp.2003.025890. View

Bookelman H, Trijbels J, Sengers R, Janssen A, Veerkamp J, STADHOUDERS A . Pyruvate oxidation in rat and human skeletal muscle mitochondria. Biochem Med. 1978; 20(3):395-403. DOI: 10.1016/0006-2944(78)90089-3. View

Ito H, Fukuda Y, Murata K, Kimura A . Transformation of intact yeast cells treated with alkali cations. J Bacteriol. 1983; 153(1):163-8. PMC: 217353. DOI: 10.1128/jb.153.1.163-168.1983. View

10.

Zara V, Palmieri F, Mahlke K, Pfanner N . The cleavable presequence is not essential for import and assembly of the phosphate carrier of mammalian mitochondria but enhances the specificity and efficiency of import. J Biol Chem. 1992; 267(17):12077-81. View

11.

Sperl W, Trijbels J, Ruitenbeek W, van Laack H, Janssen A, Kerkhof C . Measurement of totally activated pyruvate dehydrogenase complex activity in human muscle: evaluation of a useful assay. Enzyme Protein. 1993; 47(1):37-46. DOI: 10.1159/000468654. View

12.

Fiermonte G, Dolce V, Palmieri F . Expression in Escherichia coli, functional characterization, and tissue distribution of isoforms A and B of the phosphate carrier from bovine mitochondria. J Biol Chem. 1998; 273(35):22782-7. DOI: 10.1074/jbc.273.35.22782. View

13.

Huizing M, Ruitenbeek W, van den Heuvel L, Dolce V, Iacobazzi V, Smeitink J . Human mitochondrial transmembrane metabolite carriers: tissue distribution and its implication for mitochondrial disorders. J Bioenerg Biomembr. 1998; 30(3):277-84. DOI: 10.1023/a:1020501021222. View

14.

Wohlrab H . The human mitochondrial transport protein family: identification and protein regions significant for transport function and substrate specificity. Biochim Biophys Acta. 2005; 1709(2):157-68. DOI: 10.1016/j.bbabio.2005.07.003. View

15.

Palmieri L, Alberio S, Pisano I, Lodi T, Meznaric-Petrusa M, Zidar J . Complete loss-of-function of the heart/muscle-specific adenine nucleotide translocator is associated with mitochondrial myopathy and cardiomyopathy. Hum Mol Genet. 2005; 14(20):3079-88. DOI: 10.1093/hmg/ddi341. View

16.

Reichenbach J, Schubert R, Horvath R, Petersen J, Futterer N, Malle E . Fatal neonatal-onset mitochondrial respiratory chain disease with T cell immunodeficiency. Pediatr Res. 2006; 60(3):321-6. DOI: 10.1203/01.pdr.0000233252.60457.cf. View

17.

Chenna R, Sugawara H, Koike T, Lopez R, Gibson T, Higgins D . Multiple sequence alignment with the Clustal series of programs. Nucleic Acids Res. 2003; 31(13):3497-500. PMC: 168907. DOI: 10.1093/nar/gkg500. View