Associate Professor, Molecular Biology and Biochemistry
School of Biological Sciences
PH.D., University of California, Berkeley, 1980
Phone: (949) 824-7766, 4734
Fax: (949) 824-8551
University of California, Irvine
3234 McGaugh Hall
Mail Code: 3900
Irvine, CA 92697
Mitochondrial biogenesis, mitochondrial protein import, regulation of gene expression in yeast
The biogenesis of functional mitochondria is essential to the survival of all eukaryotic cells. Assembly and maintainance of this key organelle involves the coordinated expression of genes in both the nuclear and mitochondrial genomes. Mitochondrial gene products of nuclear origin must also be targeted to mitochondria then sorted to one of four intramitochondrial compartments. Currently, all of the research in our laboratory is focused on two aspects of the complex problem of mitochondrial biogenesis. First, we are defining the regulatory elements (both cis and trans) that control the expression of a pair of inversely regulated nuclear genes specifying mitochondrial proteins (COX5a and COX5b). This project utilizes the yeast Saccharomyces cerevisiae, and is designed to exploit the ease and power of molecular and genetic analysis in this organism. One particular gene of interest, ORD1 (also referred to as IXR1), encodes a transcription factor involved in the regulation of COX5b. Importantly, the Ord1 protein has also been shown to bind to platinated DNA and to confer sensitivity of yeast to the antitumor drug cisplatin.
Second, we are studying the process of protein import into mitochondria, with particular emphasis on the inner membrane. We have been, and continuue to be, involved in analyzing translocation pathways to this specific mitochondrial compartment. We are currently studying several topogenic signals that direct proteins to the inner membrane, and are also characterizing membrane proteins that may facilitate inner membrane sorting. In summary, our work on the regulation of gene expression, and on mitochondrial protein import, is designed to use a combined molecular, genetic, and biochemical approach to elucidate the molecular mechanisms that underlie fundamental biological processes.
Pam16 has an essential role in the mitochondrial protein import motor.
Frazier AE, Dudek J, Guiard B, Voos W, Li Y, Lind M, Meisinger C, Geissler A, Sickmann A, Meyer HE, Bilanchone V, Cumsky MG, Truscott KN, Pfanner N, Rehling P.
Nat Struct Mol Biol. 2004 Mar;11(3):226-33. Epub 2004 Feb 15.
Gartner, F., W. Voos, A. Querol, B.R. Miller, E. Craig, M.G. Cumsky, and N. Pfanner. 1995. Mitochondrial import of cytochrome c oxidase subunit Va characterized with yeast mutants: independence from surface receptors but requirement for the translocase function of mitochondrial hsp70. J. Biol. Chem. 270:3788-3795.
Lambert, J.R., V. W. Bilanchone, and M.G. Cumsky. 1994. The ORD1 gene encodes a transcription factor involved in oxygen regulation and is identical to IXR1, a gene that confers cisplatin sensitivity to Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 91:7345-7349.
Developmental Biology and Genetics
Mechanisms of Gene Expression