Carlos T. Moraes, Ph.D.
Professor of Neurology
Description of Research
Although mitochondrial genetics of yeast and trypanosomes has been extensively explored during the last 20 years, the study of human mitochondrial DNA (mtDNA) gained momentum in 1988 with the discovery of diseases associated with mtDNA mutations. The human mtDNA is a compact circular genome (16.6 kb) coding for components of the ATP-producing oxidative phosphorylation system. Because mtDNA-coded polypeptides are synthesized in mitochondrial-specific ribosomes, the mtDNA also codes for a set of rRNAs and tRNAs necessary for intraorganelle translation. The contribution of the mitochondrial genome to cellular respiration, though vital, is not sufficient. Dozens of nuclear-coded proteins synthesized in the cytoplasm are imported into mitochondria and assembled with mitochondrially-synthesized proteins to form a functional oxidative phosphorylation system.
Recently, mutations in the mtDNA also have been described in a large number of tumors. Dr. Moraes currently is studying the potential role of these mutations in cell signaling and invasion. Mitochondria are also major players in programmed cell death, an important determinant of tumorigenesis. A number of anti-and pro-apoptotic factors seem to mediate their functions in association with mitochondrial membranes. Dr. Moraes and his research team also are exploring the interplay between the role of cytochrome c in respiration and in stimulating apoptosis.
- Discovered colorectal tumors with stop codon mutations in the mtDNA develop a compensatory mechanism to upregulate mitochondrial respiration. The mechanism involves the upregulation of PGC-1 family members, which trigger an increase in mitochondrial biogenesis.
- Found that cytochrome c has a major role in promoting TNF-alpha mediated apoptosis in vivo
- Researchers in Dr. Moraes’ laboratory also found that the lack of respiration confers resistance to some apoptosis triggers (e.g., staurosporin) but hypersensitivity to TNF-alpha
Selected Cancer-Related Publications
- Wang X, Peralta S, Moraes CT. Mitochondrial alterations during carcinogenesis: a review of metabolic transformation and targets for anticancer treatments. Adv Cancer Res 119:127-60,2013 Read more »
- Wang X, Pickrell AM, Zimmers TA, Moraes CT. Increase in muscle mitochondrial biogenesis does not prevent muscle loss but increased tumor size in a mouse model of acute cancer-induced cachexia. PLoS One 7:e33426,2012 Read more »
- Wang X, Moraes CT. Increases in mitochondrial biogenesis impair carcinogenesis at multiple levels. Mol Oncol 5:399-409,2011 Read more »