Pxmp2 is a channel-forming protein in Mammalian peroxisomal membrane.
BACKGROUND
Peroxisomal metabolic machinery requires a continuous flow of organic and inorganic solutes across peroxisomal membrane. Concerning small solutes, the molecular nature of their traffic has remained an enigma.


RESULTS
In this study, we show that disruption in mice of the Pxmp2 gene encoding Pxmp2, which belongs to a family of integral membrane proteins with unknown function, leads to partial restriction of peroxisomal membrane permeability to solutes in vitro and in vivo. Multiple-channel recording of liver peroxisomal preparations reveals that the channel-forming components with a conductance of 1.3 nS in 1.0 M KCl were lost in Pxmp2(-/-) mice. The channel-forming properties of Pxmp2 were confirmed with recombinant protein expressed in insect cells and with native Pxmp2 purified from mouse liver. The Pxmp2 channel, with an estimated diameter of 1.4 nm, shows weak cation selectivity and no voltage dependence. The long-lasting open states of the channel indicate its functional role as a protein forming a general diffusion pore in the membrane.


CONCLUSIONS
Pxmp2 is the first peroxisomal channel identified, and its existence leads to prediction that the mammalian peroxisomal membrane is permeable to small solutes while transfer of "bulky" metabolites, e.g., cofactors (NAD/H, NADP/H, and CoA) and ATP, requires specific transporters.
Rokka
Aare
A
Department of Biochemistry, Biocenter Oulu, University of Oulu, Oulu, Finland.
Antonenkov
Vasily D
VD
Soininen
Raija
R
Immonen
Hanna L
HL
Pirilä
Päivi L
PL
Bergmann
Ulrich
U
Sormunen
Raija T
RT
Weckström
Matti
M
Benz
Roland
R
Hiltunen
J Kalervo
JK
D000818:Animals; D001483:Base Sequence; D002463:Cell Membrane Permeability; D017931:DNA Primers; D007425:Intracellular Membranes / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D020675:Peroxisomes / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D007473:Ion Channels; D008565:Membrane Proteins; C489786:Pxmp2 protein, mouse; D011994:Recombinant Proteins