Charles E. Martin
Professor

Rutgers University
Cell Biology & Neuroscience
Nelson Hall - Busch Campus
Piscataway. NJ 08855-8082
(732) 445-1633
martin@biology.rutgers.edu

Structure. function and regulation of ER membrane enzyme systems

Problems that are under study in the laboratory involve the coordinated regulation and structural organization of membrane-bound enzyme systems that are responsible for fatty acid desaturation. sterol modification and fatty acid elongation. Mutations in the regulation and function of these systems are the basis of a number of devastating human diseases. including atherosclerosis and severe neurological disorders. We have identified two independent fatty acid and oxygen-responsive. regulatory mechanisms that control this complex system of enzymes in Saccharomyces. One works by controlling transcription and the other works at the level of mRNA stability. Both systems are activated by membrane-bound protein sensors that are cleaved by a unique ubiquitin-mediated proteolysis. This releases soluble fragments of the sensor proteins that are translocated to the nucleus where they act to control gene expression.

We are currently involved in studies that will identify and determine the functions of the fatty acid and molecular oxygen "detectors" and signal transduction components of these regulatory circuits that activate transcription and control mRNA stability in both Saccharomcyes and Candida albicans.

Selected Publications

Martin CE, Oh CS, Jiang Y. (2007) Regulation of long chain unsaturated fatty acid synthesis in yeast. Biochim Biophys Acta. 1771(3):271-85.

Oh. C-S.. and C. E. Martin. (2006) Candida albicans Spt23p controls the expression of the Ole1p D9 fatty acid desaturase and regulates unsaturated fatty acid biosyntheses. J Biol Chem. 281(11):7030-9.

Boumann. H.A.. Gubbens. J.. Koorengevel. M.C.. Oh. C-S.. Martin. C.E.. Heck. A.J.R.. Patton-Vogt. J.. Henry. S.A.. deKruijff. B. and A.I.P.M. de Kroon. Depletion of phosphatidylcholine in yeast induces shortening and increased saturation of the lipid acyl chains. Evidence for regulation of intrinsic membrane curvature in a eukaryote. (2006) Mol. Biol. Cell. 17:1106-1017

Kandasamy. P.. Vemula. M. Oh. C.S.. Chellappa. R.. Martin. C.E. (2004) Regulation of unsaturated fatty acid biosynthesis in Saccharomyces. The ER membrane protein. Mga2p. a transcription activator of the OLE1 gene. regulates the stability of the OLE1 mRNA through exosome-mediated mechanisms. J. Biol. Chem 279 36586 - 36592.

Vemula. M.. Kandasamy. P.. Oh. C-S. Chellappa. R. Gonzalez. C.I.. Martin. C.E. (2003) Maintenance and regulation of mRNA stability of the Saccharomyces cerevisiae OLE1 gene requires multiple elements within the transcript that act through translation-independent mechanisms. J. Biol. Chem. 278:45269-45279.

Jiang. Y. Vasconcelles. M. J. Wretzel. S. Light. A.. C. E. Martin. C-S. Oh. Goldberg. M. A. (2002) Mga2p processing by hypoxia and unsaturated fatty acids in S. cerevisiae: Impact on LORE-dependent gene expression. Eukaryotic Cell 1 481-490.

Jiang. Y. Vasconcelles. M. J. Wretzel. S. Light. A.. C. E. Martin. Goldberg. M. A. (2001) is involved in the LORE-dependent hypoxic induction of genes in S. cerevisiae. Molecular and Cell Biology 21:6161-6969.

Chellapa. R.. Kandasamy. P.. Oh. C-S. Jiang. Y.. Vemula. M.. and Martin. C.E. (2001) The membrane proteins Spt23p and Mga2p. play distinct roles in the activation of Saccharomyces cerevisiae OLE1 gene expression. J. Biol. Chem. 276:43548-43556.

Vasconcelles. M. Jiang. Y. McDaid. K.. Gilooly. L.. Wretzel. S.. Porter. D.L.. Charles Martin. and Goldberg. M. (2001) Identification and characterization of a low oxygen response element (LORE) involved in the hypoxic induction of a family of S. cerevisiae genes. Implications for the conservation of oxygen sensing in eukaryotes. J. Biol. Chem. 276: 14374-14384.

Kohlwein. S.D.. Eder. S. Chan-Seok Oh. Charles E. Martin. Gable. K. Bacikova. D. and Dunne. T. (2000). Tsc13 is required for fatty acid elongation and localizes to a novel structure at the nuclear/vacuolar interface in Saccharomyces cerevisiae. Molecular and Cellular Biology 21:109-125

Choi. J-Y and Martin. C.E.(1999) The Saccharomyces cerevisiae FAT1 gene encodes an acyl CoA synthetase that is required for maintenance of very long chain fatty acid levels. Journal of Biological Chemistry 274 . 4671-4683.

Mitchell. A.G. and Martin. C.E. (1997). Fah1p. a Saccharomyces cerevisiae cytochrome b5 fusion protein. and its arabidopsis thaliana homolog that lacks the cytochrome b5 domain both function in the a-hydroxylation of sphingolipid-associated very long chain fatty acids. J. Biol Chem. 272(45): 28281-28288.

Oh. C-S. Toke. D.A.. Mandala. S.. and Martin. C.E. (1997). ELO2 and ELO3. homologues of the Saccharomyces cerevisiae ELO1 gene. are involved in fatty acid elongation and are required for sphingolipid formation. Journal of Biological Chemistry 272:17376-17384.

Gonzalez. C.I. and Martin. C.E. (1996). Fatty acid-responsive control of mRNA stability. Unsaturated fatty acid-induced degradation of the Saccharomyces OLE1 transcript.. J. Biol. Chem. 271 (42): 25801-25809.

Toke. D.A. and Martin. C.E. (1996). Isolation and Characterization of a gene affecting fatty acid elongation in Saccharomyces cerevisiae. J. Biol. Chem. 271:18413-18422.

Choi. J-Y.. Stukey. J.. Hwang. S-Y. and Martin. C.E. (1996). Regulatory elements that control transcription activation and unsaturated fatty acid-mediated repression of the Saccharomyces cerevisiae OLE1 Gene. J. Biol. Chem. 271:3581-3589.

Mitchell. A.G. and Martin. C. E. (1995). A novel cytochrome b5-like domain is linked to the carboxyl terminus of the Saccharomyces cerevisiae -9 fatty acid desturase. J. Biol. Ched. 270:29766-29772.