The structure-based single Q tunnel models of complex I have been questioned. It has been argued that there are alternative cavities present in complex I that may allow diffusion of Q or even larger molecules to the N2 cluster and take part in the redox reactions and catalyze proton pumping . Structural and simulation data indeed support the existence of additional tunnels and cavities in complex I . For instance, atomistic MD simulations of short-tailed Q analogues modeled in the Q tunnel showed that they can diffuse out to the bulk N phase via cavities alternate to the canonical Q tunnel . To test the hypothesis that there indeed are alternative Q diffusion routes, it would be desirable to perform site-directed mutagenesis of cavity-lining conserved residues and study complex I activity and binding affinity of Q and its analogues.