TPP via a lysine linker showed a stronger effect than a-CEHC alone. These results confirm the importance of mitochondria targeting as a strategy to diminish mitochondrial oxidative stress. In an effort to investigate if the TPP + conjugation to a-CEHC via a lysine linker would increase mitochondrial targeting, an in vivo experiment was performed. Since TPP+ conjugates are orally bioavailable when fed to mice, highly insulin resistant db/db mice were provided with 200 mM of the MitoCEHC in their drinking water. Although there is no direct correlation of dosing of vitamin E-like compounds between mice and humans, MitoCEHC doses selected in this study were based on maximal MitoVit E dosing of mice. Therefore we chose the lowest dose that would still target the mitochondria for these studies. After two weeks of providing mice with MitoCEHC in their drinking water, their plasma was collected and hearts were harvested to isolate myocardial mitochondria. The isolated mitochondria were then lysed. The concentrations of MitoCEHC in the collected samples were simultaneously measured against a concentration standard curve. The retention times for the MitoCEHC standard and samples are shown as 13.9 and 13.6 minutes respectively. The untreated mice showed no trace of MitoCEHC in the isolated mitochondria or plasma. In addition to its antioxidant potential in cell lines, MitoCEHC accumulated in the mitochondria in vivo. More in vivo work still needs to be performed to test the effect of MitoCEHC on mitochondrial superoxide generation, oxygen consumption, and ATP production. In summary, the conjugation of a-CEHC to TPP+ was achieved using a fast and efficient method involving a lysine linker and solid phase synthesis. The conjugated product was effective in lowering oxidative stress in BAECs and targeting the mitochondria in type 2 diabetic db/db mice. The antioxidant effect of this drug may be clinically relevant and could be used to treat diseases related to oxidative stress such as cardiovascular disease. Vision is initiated in the retina where light is captured by the outer segment organelle of photoreceptor cells. The outer segment is a modified primary cilium that contains large quantities of proteins involved in visual signal transduction. Similar to all cilia, the outer segment lacks the machinery required to synthesize proteins and therefore relies on the import of proteins produced in the cell body of photoreceptor cells. The importance of accurate protein targeting to the outer segment is highlighted by observations that defects in protein targeting result in retinal degenerative diseases. Membrane proteins destined for the outer segment are synthesized in the endoplasmic reticulum, amps reported evolved adaptively accelerated rate amino acid transported through the Golgi, and then sorted at the trans-Golgi network into transport vesicles specifically directed to the outer segment. The fidelity of sorting is guided by targeting signals, which are short stretches of amino acid residues encoding protein localization information. These targeting signals often reside within a protein��s cytoplasmic domain and are deciphered by protein sorting complexes present at the trans-Golgi. Only two targeting signals responsible for directing membrane proteins to the outer segment have been reported thus far. One signal is VXPX, which is shared by rhodopsin, cone opsins, and the photoreceptorspecific retinol dehydrogenase, as well as several other proteins targeted to primary and sensory cilia in other cell types.