Organellar Na+/H+ exchangers: novel players in organelle pH regulation and their emerging functions

Biochemistry. 2011 Feb 1;50(4):443-50. doi: 10.1021/bi101082e. Epub 2010 Dec 30.


Mammalian Na+/H+ exchangers (NHEs) play a fundamental role in cellular ion homeostasis. NHEs exhibit an appreciable variation in expression, regulation, and physiological function, dictated by their dynamics in subcellular localization and/or interaction with regulatory proteins. In recent years, a subgroup of NHEs consisting of four isoforms has been identified, and its members predominantly localize to the membranes of the Golgi apparatus and endosomes. These organellar NHEs constitute a family of transporters with an emerging function in the regulation of luminal pH and in intracellular membrane trafficking as expressed, for example, in cell polarity development. Moreover, specific roles of a variety of cofactors, regulating the intracellular dynamics of these transporters, are also becoming apparent, thereby providing further insight into their mechanism of action and overall functioning. Interestingly, organellar NHEs have been related to mental disorders, implying a potential role in the brain, thus expanding the physiological significance of these transporters.

Publication types

  • Review

MeSH terms

  • Acid-Base Equilibrium / genetics
  • Acid-Base Equilibrium / physiology
  • Animals
  • Cell Line, Tumor
  • Disease Models, Animal
  • Humans
  • Hydrogen-Ion Concentration
  • Intracellular Fluid / chemistry
  • Intracellular Fluid / metabolism
  • Intracellular Fluid / physiology
  • Mental Disorders / genetics
  • Mental Disorders / metabolism
  • Mental Disorders / physiopathology
  • Mice
  • Organelles / chemistry*
  • Organelles / genetics
  • Organelles / metabolism
  • Organelles / physiology*
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / deficiency
  • Protein Isoforms / physiology
  • Protein Transport / genetics
  • Protein Transport / physiology
  • Sodium-Hydrogen Exchangers / biosynthesis
  • Sodium-Hydrogen Exchangers / chemistry
  • Sodium-Hydrogen Exchangers / genetics
  • Sodium-Hydrogen Exchangers / metabolism
  • Sodium-Hydrogen Exchangers / physiology*
  • Tissue Distribution / genetics
  • Tissue Distribution / physiology


  • NHE9 protein, mouse
  • Protein Isoforms
  • SLC9A6 protein, human
  • SLC9A7 protein, human
  • SLC9A8 protein, human
  • Sodium-Hydrogen Exchangers