SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

T U M O R C E L L B I O L O G Y P R O G R A M
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 nuclearcoded
proteins synthesized in the cytoplasm are
imported into mitochondria and assembled with
mitochondrially synthesized proteins to form a
functional oxidative phosphorylation system.
Recently, defects in mitochondrial function
also have been associated with some forms of
tumors. 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 also are major players in programmed
cell death, an important determinant
of tumorigenesis. A number of anti- and proapoptotic
factors seem to mediate their functions
in association with mitochondrial membranes.
Dr. Moraes and his colleagues also are exploring
the role of cytochrome c in stimulating apoposis.
SELECTED PUBLICATIONS
2002
Moraes, CT, Srivastava, S, Kirkinezos, I, Oca-
Cossio, J, van Waveren, C, Woischnick, M, and
Diaz, F. Mitochondrial DNA structure and function.
International Review of Neurobiology 53:3-
23, 2002.
Moraes, CT. Studying mitochondria of animal
cells. Methods 26:291, 2002.
Woischnik, M and Moraes, CT. Pattern of organization
of human mitochondrial pseudogenes in
the nuclear genome. Genome Research 12:885-
93, 2002.
Lanza, RP, Chung, HY, Yoo, JJ, Wettstein, PJ,
Blackwell, C, Borson, N, Hofmeister, E, Schuch,
G, Soker, S, Moraes, CT, West, MD, and Atala,
A. Generation of histocompatible tissues using
nuclear transplantation. Nature Biotechnology
20:689-96, 2002.
Diaz, F, Bayona-Bafaluy, MP, Rana, M, Mora, M,
Hao, H, and Moraes, CT. Human mitochondrial
DNA with large deletions repopulates organelles
faster than full-length genomes under relaxed
copy number control. Nucleic Acids Research
30:4626-33, 2002.
2003
Manfredi, G, Kwong, JQ, Oca-Cossio, JA,
Woischnik, M, Gajewski, CD, Martushova, K,
D’Aurelio, M, Friedlich, AL, and Moraes, CT.
BCL-2 improves oxidative phosphorylation and
modulates adenine nucleotide translocation in
mitochondria of cells harboring mutant mtDNA.
Journal of Biological Chemistry 278:5639-45,
2003.
Bacman, SR, Atencio, DP, and Moraes, CT. Decreased
mitochondrial tRNALys steady-state levels
and aminoacylation are associated with the
pathogenic G8313A mitochondrial DNA mutation.
Biochemical Journal 374:131-36, 2003.
Bayona-Bafaluy, MP, Manfredi, G, and Moraes,
CT. A chemical enucleation method for the
transfer of mitochondrial DNA to rho(o) cells.
Nucleic Acids Research 31:e98, 2003.
HIGHLIGHTS/DISCOVERIES
• Discovered that cells with defective mitochondrial
respiration can be more resistant to cell
death. This is a counterintuitive concept since it
was previously thought that the less energy a
cell has, the easier it is to kill it. Programmed
cell death, however, does require a considerable
amount of ATP (energy) to occur. These findings
may explain the presence of mtDNA mutations
in some cancers.
• Demonstrated that mitochondrial defects
stimulate the production of metalloproteases,
which in turn, promote tissue invasion.
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UM/Sylvester Comprehensive Cancer Center Scientific Report 2004