Identification of mitochondrial genome concatemers in AIDS-associated lymphomas and lymphoid cell lines

Bedoya, Felipe; Medveczky, Maria M.; Lund, Troy C.; Perl, Andras; Horvath, Joseph; Jett, Stephen D.; Medveczky, Peter G.

doi:10.1016/j.leukres.2009.03.012

« Previous Next »Leukemia Research
Volume 33, Issue 11 , Pages 1499-1504, November 2009

Identification of mitochondrial genome concatemers in AIDS-associated lymphomas and lymphoid cell lines

Felipe Bedoya
- Department of Molecular Medicine, College of Medicine, University of South Florida, Tampa, FL 33612, United States
- These authors contributed equally to this work.
Maria M. Medveczky
- Department of Molecular Medicine, College of Medicine, University of South Florida, Tampa, FL 33612, United States
- These authors contributed equally to this work.
Troy C. Lund
- Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States
Andras Perl
- Department of Medicine, State University of New York, Syracuse, NY, United States
Joseph Horvath
- Hemispherx Biopharma, Inc., New Brunswick, NJ, United States
Stephen D. Jett
- Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, NM, United States
Peter G. Medveczky
- Department of Molecular Medicine, College of Medicine, University of South Florida, Tampa, FL 33612, United States
- Corresponding author. Fax: +1 813 396 9188.

Received 13 December 2008; received in revised form 11 March 2009; accepted 12 March 2009. published online 07 March 2011.

Abstract

Since most oncogenic viruses persist as extrachromosomal covalently closed circular DNA (cccDNA) in tumor cells, we developed an assay to visualize and identify cccDNA in primary lymphomas. We identified concatemers of the mitochondrial genome in all samples analyzed, but not in normal lymphocytes. One AIDS-associated lymphoma (EL) was further studied in detail as its mitochondrial genome consisted of tandem head-to-tail duplications. Insertion of C-residues was noted near the origin of replication of EL mtDNA. EL cells responded weakly to Fas-apoptotic stimulus, displayed reduced mitochondrial activity and mass, and produced higher levels of reactive oxygen intermediates. Screening of several AIDS-associated lymphomas and established lymphoid cell lines also revealed the presence of mitochondrial genome concatemers consisting of interlinked monomer molecules. Taken together, our results suggest that formation of mtDNA concatemers is associated with oncogenic transformation in lymphoid cells.

Abbreviations: MtDNA, mitochondrial DNA, CSBII, conserved sequence box II, cccDNA, covalently closed circular DNA

Keywords: Mitochondrial DNA concatemers, AIDS-associated lymphomas, Oncogenic transformation, Leukemogenesis, Mitochondria