Similar to the debated role of SQ in the catalytic mechanism of complex I, the role of one active site tyrosine (Tyr144 from NDUFS2 subunit of Y. lipolytica complex I) also remains perplexing. Several lines of data point to the role of Tyr144 in trapping the Q head group near the N2 cluster (site 1) by forming a direct hydrogen bond to it. However, in Y. lipolytica structures, the Q head group has always been resolved closer to site 2, thus, a direct hydrogen bond between Q and tyrosine has not been observed. Recently, molecular simulations showed that Q can indeed bind to site 1 also in Y. lipolytica complex I with a hydrogen bond to Tyr144 (60), similar to the observation from structures of complex I from other species . Previously, computer simulations have suggested that Tyr144 may provide a proton upon Q reduction . However, site directed mutagenesis data show that there is a residual Q reductase activity and proton pumping even upon mutation of Tyr144 to phenylalanine , arguing against its function as a proton donor. In the mechanistic proposal discussed below, the role this active site tyrosine is discussed (see section 6).