Human Na+/H+ exchanger isoform 6 is found in recycling endosomes of cells, not in mitochondria

Christopher L. Brett, Ying Wei, Mark Donowitz, Rajini Rao

Research output: Contribution to journalArticlepeer-review

130 Scopus citations


Since the discovery of the first intracellular Na+/H+ exchanger in yeast, Nhx1, multiple homologs have been cloned and characterized in plants. Together, studies in these organisms demonstrate that Nhxl is located in the prevacuolar/vacuolar compartment of cells where it sequesters Na+ into the vacuole, regulates intravesicular pH, and contributes to vacuolar biogenesis. In contrast, the human homolog of Nhx1, Na+/H+ exchanger isoform 6 (NHE6), has been reported to localize to mitochondria when transiently expressed as a fusion with green fluorescent protein. This result warrants reevaluation because it conflicts with predictions from phylogenetic analyses. Here we demonstrate that when epitope-tagged NHE6 is transiently expressed in cultured mammalian cells, it does not colocalize with mitochondrial markers. It also does not colocalize with markers of the lysosome, late endosome, trans-Golgi network, or Golgi cisternae. Rather, NHE6 is distributed in recycling compartments and transiently appears on the plasma membrane. These results suggest that, like its homologs in yeast and plants, NHE6 is an endosomal Na+/H+ exchanger that may regulate intravesicular pH and volume and contribute to lysosomal biogenesis.

Original languageEnglish (US)
Pages (from-to)C1031-C1041
JournalAmerican Journal of Physiology - Cell Physiology
Issue number5 51-5
StatePublished - 2002


  • Intracellular NHE
  • Intraendosomal pH
  • Nhx1

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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