TMEM175 Is an Organelle K(+) Channel Regulating Lysosomal Function

Cell. 2015 Aug 27;162(5):1101-12. doi: 10.1016/j.cell.2015.08.002.


Potassium is the most abundant ion to face both plasma and organelle membranes. Extensive research over the past seven decades has characterized how K(+) permeates the plasma membrane to control fundamental processes such as secretion, neuronal communication, and heartbeat. However, how K(+) permeates organelles such as lysosomes and endosomes is unknown. Here, we directly recorded organelle K(+) conductance and discovered a major K(+)-selective channel KEL on endosomes and lysosomes. KEL is formed by TMEM175, a protein with unknown function. Unlike any of the ∼80 plasma membrane K(+) channels, TMEM175 has two repeats of 6-transmembrane-spanning segments and has no GYG K(+) channel sequence signature-containing, pore-forming P loop. Lysosomes lacking TMEM175 exhibit no K(+) conductance, have a markedly depolarized ΔΨ and little sensitivity to changes in [K(+)], and have compromised luminal pH stability and abnormal fusion with autophagosomes during autophagy. Thus, TMEM175 comprises a K(+) channel that underlies the molecular mechanism of lysosomal K(+) permeability.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Endosomes / metabolism*
  • Gene Knockout Techniques
  • Humans
  • Intracellular Membranes / metabolism
  • Lysosomes / metabolism*
  • Mice
  • Molecular Sequence Data
  • Patch-Clamp Techniques
  • Phagosomes / metabolism
  • Potassium / metabolism*
  • Potassium Channels / chemistry
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Sequence Alignment


  • Potassium Channels
  • TMEM175 protein, human
  • TMEM175 protein, mouse
  • Potassium