Membrane Permeability to Pyruvate Pyruvate seems to pass easily through the outer membrane of the mitochondrion but has difficulty entering the inner membrane (and gets in by H+ symport). I have two questions: (1) what property of pyruvate disallows it from passing through the inner membrane? Is it its charge? and (2) what structural differences are there between the outer and inner membranes of the mitochondrion that create their disparate permeabilities to pyruvate?

Pyruvate is negatively charged and quite polar, which makes it unfavourable to diffuse directly through any membrane. The outer mitochondrial membrane contains porins), which allow small molecules, like pyruvate, to passively diffuse through. Specifically, pyruvate uses voltage dependent anion channels. The inner mitochondrial membrane lacks such channels and depends on active transport by the long anticipated but only recently discovered mitochondrial pyruvate carrier (Herzig et al. and Bricker et al., 2012).