# Longer Ubiquinone Side Chains Contribute to Enhanced Farnesol Resistance in Yeasts
## 4 Discussion
albicans_, it is primarily non-pathogenic and it lacks the diverse morphogenic forms as in _C. albicans_. Because _C. albicans_ uses farnesol as a virulence factor in pathogenesis [4; 5], it would be interesting to make similar mutants of _C. albicans_, forced to use isoprenoid chain lengths varying from UQ5 to UQ10, and then compare their respective levels of pathogenicity in mouse models of disseminated candidiasis. However, the construction of respiratory deficient mutants in _C. albicans_ could be challenging because respiratory deficiency is usually lethal in almost all species of Candida [40]. The wide distribution of UQs in membranes of Golgi, lysosomes, peroxisomes, and cell membranes other than mitochondria suggests UQ may be involved in roles other than electron transfer as reviewed by [41; 42; 43]. The antioxidant function of UQ is well studied in that it protects against lipid peroxidation in the membrane [44]. All these mechanisms are attributable to the redox active benzoquinone ring of UQ. However, the biological significance of the ubiquinone side chain length is reported only intermittently and no molecular or signaling mechanisms have been suggested for those observations. [PERSON] et al. [32] proposed that the UQ chain length was determined by the membrane hydrophobicity of an organism while [PERSON] and [PERSON] [45] suggested that UQ chain length aids in the localization of UQ within phospholipid bilayers with longer chain lengths permitting efficient transmembrane movement of hydrogen atoms [45]. Most interestingly, _E. coli_ was recently found to accumulate far greater levels of its native UQ8 (110-fold) in response to osmotic stress (750 mM NaCl) [46]. The extra UQ8 increased membrane stability quite independent of its role in respiration or radical scavenging. [PERSON] and [PERSON] [46] concluded that the osmoprotection provided by UQ8 was conveyed by the octaprenyl tail and not by the benzoquinone moiety, and that only chains of sufficient length were able to provide osmotolerance. They also suggested that UQ\({}_{n}\) with n > 8 isoprenoid units could provide mechanical stabilization of cellular membranes but no further mechanisms for this osmoprotection have yet been identified. Due to the variety of environmental niches where _E. coli_ can be found [47], this physical mechanism could be another evolutionary adapted trait in these bacteria to increase their fitness in both host-associated and non-host associated habitats [47]. With our observation of farnesol protection conferred by longer UQ side chain length, we conclude that having different isoprenoid side chain lengths in different organisms is another example of niche-adapted evolutionary mechanisms by which chemical diversity is generated in nature in order to provide a selective advantage. The importance of farnesol as a virulence factor for _C. albicans_ is such that using UQ9 is just one of the structural adaptations this successful pathogen has made. Another possible adaptation is the pressure farnesol provides for maintaining _C. albicans_ as a diploid rather than as a haploid [48]. In addition to acting as a virulence factor [4; 5] and signaling molecule [2; 3], farnesol has some detergent-like activity. Another example of the complexity of cellular adaptations to detergents has been studied in enteric bacteria growing in the presence of 5-10% sodium dodecyl sulfate (SDS). For _Enterobacter cloace_ and _E. coli_, their structural adaptations to SDS occur in at least five subcellular locations [49; 50]. Moving progressively inwards, these were (i) a negatively charged capsule provided by the presence of colonic acid [49]; (ii) the outer membrane as a necessary barrier; (iii) synthesis of negatively charged membrane-derived oligosaccharides (MDOs) in the periplasm [50]; (iv) the cytoplasmic membrane as the site of efflux pumps able to extrude SDS; and (v) the cytoplasm itself in the form of the ClpP, ClpX, and ClpB proteases necessary to recycle proteins which have been damaged by the SDS [49].