Identification of a mitochondrial Na+/H+ exchanger

The electroneutral exchange of protons for Na + and K + across the mitochondrial inner membrane contributes to organellar volume and Ca 2+ homeostasis. The molecular nature of these transporters remains unknown. In this report, we characterize a novel gene (YDR456w; renamed NHA2 ) in Saccharomyces c...

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Bibliographic Details
Published in:The Journal of biological chemistry 1998-03, Vol.273 (12), p.6951-6959
Main Authors: Numata, M, Petrecca, K, Lake, N, Orlowski, J
Format: Article
Language:English
Subjects:
Amino Acid Sequence
AMINO ACID SEQUENCES
Base Sequence
BINDING PROTEINS
BIOCHEMISTRY
BIOCHIMIE
BIOLOGICAL DIFFERENCES
BIOQUIMICA
CATION
CATIONES
CATIONS
CELL MEMBRANES
CHEMICAL COMPOSITION
COMPOSICION QUIMICA
COMPOSITION CHIMIQUE
CRECIMIENTO
CROISSANCE
CYTOCHEMISTRY
DELETIONS
DIFERENCIAS BIOLOGICAS
DIFFERENCE BIOLOGIQUE
DNA, Complementary
FENOTIPOS
GENE
GENES
GROWTH
HeLa Cells
HIDROGENO
Humans
HYDROGEN
HYDROGENE
ION
ION TRANSPORT
IONES
IONS
MEMBRANAS CELULARES
MEMBRANE CELLULAIRE
MITOCHONDRIA
Mitochondria - metabolism
MITOCHONDRIE
MITOCONDRIA
Molecular Sequence Data
MUTACION
MUTANT
MUTANTES
MUTANTS
MUTATION
NUCLEOTIDE SEQUENCE
PHENOTYPE
PHENOTYPES
PROTEINAS AGLUTINANTES
PROTEINE DE LIAISON
SACCHAROMYCES CEREVISIAE
Saccharomyces cerevisiae - metabolism
SECUENCIA NUCLEOTIDICA
Sequence Homology, Amino Acid
SEQUENCE NUCLEOTIDIQUE
SODIO
SODIUM
Sodium-Hydrogen Exchangers - genetics
Sodium-Hydrogen Exchangers - metabolism
SPECIES DIFFERENCES
Subcellular Fractions - metabolism
SUPERVIVENCIA
SURVIE
SURVIVAL
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Summary:The electroneutral exchange of protons for Na + and K + across the mitochondrial inner membrane contributes to organellar volume and Ca 2+ homeostasis. The molecular nature of these transporters remains unknown. In this report, we characterize a novel gene (YDR456w; renamed NHA2 ) in Saccharomyces cerevisiae whose deduced protein sequence is homologous to members of the mammalian Na + /H + exchanger gene family. Fluorescence microscopy showed that a Nha2-green fluorescent protein chimera colocalizes with 4′,6-diamidino-2-phenylindole staining of mitochondrial DNA. To assess the function of Nha2, we deleted the NHA2 gene by homologous disruption and found that benzamil-inhibitable, acid-activated 22 Na + uptake into mitochondria was abolished in the mutant strain. It also showed retarded growth on nonfermentable carbon sources and severely reduced survival during the stationary phase of the cell cycle compared with the parental strain, consistent with a defect in aerobic metabolism. Sequence comparisons revealed that Nha2 has highest identity to a putative Na + /H + exchanger homologue (KIAA0267; renamed NHE6) in humans. Northern blot analysis demonstrated that NHE6 is ubiquitously expressed but is most abundant in mitochondrion-rich tissues such as brain, skeletal muscle, and heart. Fluorescence microscopy showed that a NHE6-green fluorescent protein chimera also accumulates in mitochondria of transfected HeLa cells. These data indicate that NHA2 and NHE6 encode homologous Na + /H + exchangers and suggest they may be important for mitochondrial function in lower and higher eukaryotes, respectively.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.273.12.6951