Department of Pharmacology and Toxicology
B.S., Fundan University, CHINA
Faculty Advisor: Dr. Wai-Meng Kwok
Phone: (414) 456-5625
The voltage-dependent anion channel, VDAC-1, is the most abundant protein on the outer membrane of mitochondria (OMM), and is the main conduit for the exchange of metabolites between the OMM and cytosol. Therefore, VDAC-1 is a crucial component involved in cell survival. An intriguing property of VDAC-1 is its ability to conduct metabolites and anions in its high conductance "open" state and cations such as calcium and sodium in its low conductance "closed" state. These conformational changes in VDAC-1 are modulated by phosphorylation: phosphorylation promotes the "closed" state and dephosphorylation promotes the "open" state. Although VDAC-1 has been implicated in protecting the heart against ischemia-reperfusion injury, determining whether the phosphorylation or dephosphorylation of VDAC-1 is the underlying critical step has been elusive. My work is to characterize the functional change of residue-specific phosphorylation on VDAC-1 using site-directed mutagenesis and protein expression combined with planar lipid bilayer system and relate to its role in cell survival, and ultimately cardioprotection using mitochondrial bioenergetics and confocal microscopy.