Very recently, a high-resolution structure of complex I from Arabidopsis thaliana revealed a potential path to the P side in the ND2 antiporter-like subunit . Interestingly, this pathway does not link the conserved terminal lysine residue (Lys383 in Y. lipolytica) to the P side of the membrane as one would have expected, but instead it links a network of water molecules and polar amino acid residues (Ser409 and Tyr412, A. thaliana numbering) to form the connectivity towards the P side, originating at the penultimate non conserved histidine residue (His326). Even though the pathway consists of polar amino acid residues, sequence analysis reveals these residues are not strictly conserved, neither in ND2-like subunits nor in between ND2/4/5 subunits, and additionally not in the related Mrp antiporter family. It is interesting to note that this pathway is seen in a I+III2 supercomplex, which causes a bend in complex I membrane domain . Helix bending/tilting, together with the presence of a detergent molecule in Arabidopsis complex I, seems to alter the section of the broken TMH12 that is closer to the P side resulting in an excess space created for water molecules forming the route. Interestingly, this novel position of TMH12 has not yet been seen in any of the other complex I structures, either mammalian, bacterial or fungal. This, however, does not discount the possibility that such a structural change may also occur in unassociated complex I during turnover. Thus, the P side paths in ND2 and ND4 cannot be ruled out at this stage. Indeed, biochemical data indicate that enzyme lacking the distal part of the membrane arm including ND5 pumps protons . Thus, further computational and experimental support is needed to prove/disprove that P side pathways form in ND2/4 subunits.