Mitochondrial function is dependent upon mitochondrial protein import (MPI), a complex process that transports nuclear-encoded proteins into mitochondria. Little is known about MPI in neurons. We examined the effects of Resveratrol (RSV), a polyphenolic antioxidant compound from grapes, on MPI in a neuronal cell model, differentiated PC12 cells. RSV (50µM, 24h) increased levels of mtGFP, a nuclear encoded mitochondrially targeted green fluorescent protein, and mtHsp70, a physiological mitochondrial heat shock protein, in mitochondria. In addition RSV also increased levels of Tom20, a key translocase of the outer mitochondrial membrane. The RSV mediated increases in mitochondrial proteins were independent of increases in mitochondrial mass or changes in intramitochondrial degradation. RSV also reduced mitochondria membrane potential and decreased basal levels of reactive oxygen species. Taken together, these findings show that RSV increases MPI and that this effect may be an important mechanism in the reported neuroprotective effects of RSV.

Mitochondrial function is dependent upon mitochondrial protein import (MPI), a complex process that transports nuclear-encoded proteins into mitochondria. Little is known about MPI in neurons. We examined the effects of Resveratrol (RSV), a polyphenolic antioxidant compound from grapes, on MPI in a neuronal cell model, differentiated PC12 cells. RSV (50µM, 24h) increased levels of mtGFP, a nuclear encoded mitochondrially targeted green fluorescent protein, and mtHsp70, a physiological mitochondrial heat shock protein, in mitochondria. In addition RSV also increased levels of Tom20, a key translocase of the outer mitochondrial membrane. The RSV mediated increases in mitochondrial proteins were independent of increases in mitochondrial mass or changes in intramitochondrial degradation. RSV also reduced mitochondria membrane potential and decreased basal levels of reactive oxygen species. Taken together, these findings show that RSV increases MPI and that this effect may be an important mechanism in the reported neuroprotective effects of RSV.

Organosulfur compounds have been used by humans for centuries and played a pivotal role in shaping our history. The chemistry presented herein deals primarily with three distinct organic transformations involving organosulfur species. The three transformations are used in tandem to complete the synthesis of natural products. The first chapter examines a new diastereoselective alkylation reaction of sulfenate anions with stereoinduction provided by chiral amino iodides. A series of β-amino sulfoxides are accessed in good yields and selectivities from alkylations with the corresponding lithium arene- and E-1-alkenesulfenate anions. The relative reactivity of different electrophiles towards a selection of lithium sulfenate anions was also evaluated by performing competition experiments. In the second chapter 1,2-dibromotetrachloroethane (C2Br2Cl4) was evaluated as a more economical halogenating agent for the in-situ Ramberg-Bäcklund rearrangement (RBR). A series of trans-stilbenoids were successfully synthesized using this protocol in excellent yields. The new RBR system also worked well for dialkyl and cyclic substrates, but the reaction was plagued by polyhalogenation for hexyl benzyl sulfone. The methodology was extended to the formal total synthesis of natural polyphenol E-resveratrol. Chapter three investigates asymmetric aza-Michael reactions of chiral β-amino sulfoxides/sulfones to synthesize thiomorpholine S-oxides and S,S-dioxides, respectively. Remarkably, cyclizations of the β-amino sulfoxides provide the trans- 3,5-substituted heterocycles, while the β-amino sulfones provide the complementary cis-3,5-substituted heterocycles. The aza-Michael chemistry was exploited along with the sulfenate and RBR protocols to access two ant venom alkaloids. / NSERC