The Mitochondrial Genome Is a “Genetic Sanctuary” during the Oncogenic Process

Since Otto Warburg linked mitochondrial physiology and oncogenesis in the 1930s, a number of studies have focused on the analysis of the genetic basis for the presence of aerobic glycolysis in cancer cells. However, little or no evidence exists today to indicate that mtDNA mutations are directly responsible for the initiation of tumor onset. Based on a model of gliomagenesis in the mouse, we aimed to explore whether or not mtDNA mutations are associated with the initiation of tumor formation, maintenance and aggressiveness. We reproduced the different molecular events that lead from tumor initiation to progression in the mouse glioma. In human gliomas, most of the genetic alterations that have been previously identified result in the aberrant activation of different signaling pathways and deregulation of the cell cycle. Our data indicates that mitochondrial dysfunction is associated with reactive oxygen species (ROS) generation, leading to increased nuclear DNA (nDNA) mutagenesis, but maintaining the integrity of the mitochondrial genome. In addition, mutational stability has been observed in entire mtDNA of human gliomas; this is in full agreement with the results obtained in the cancer mouse model. We use this model as a paradigm of oncogenic transformation due to the fact that mutations commonly found in gliomas appear to be the most common molecular alterations leading to tumor development in most types of human cancer. Our results indicate that the mtDNA genome is kept by the cell as a “genetic sanctuary” during tumor development in the mouse and humans. This is compatible with the hypothesis that the mtDNA molecule plays an essential role in the control of the cellular adaptive survival response to tumor-induced oxidative stress. The integrity of mtDNA seems to be a necessary element for responding to the increased ROS production associated with the oncogenic process

Leishmaniasis transmission in an ecotourism area: potential vectors in Ilha Grande, Rio de Janeiro State, Brazil

BACKGROUND: The south coast of Rio de Janeiro State, in Brazil, is endemic for cutaneous and visceral leishmaniases and is frequently visited by tourists from different parts of the world. Since the complex epidemiology of leishmaniases demands local studies, the goal of this study was to investigate the phlebotomine sand fly fauna and leishmaniases transmission in Ilha Grande, an ecotourism area of Angra dos Reis municipality. METHODS: Sand fly fauna was sampled in three monitoring stations using HP light traps in domiciles, peridomiciles and forests. Species abundance was evaluated by the Index of Species Abundance. A Leishmania natural infection survey was done using multiplex PCR and dot blot hybridization. RESULTS: During 15 consecutive months of sand fly monitoring, 1093 specimens from 16 species were captured. The potential leishmaniases vectors found were Lutzomyia (Nyssomyia) intermedia, L. migonei, L. (N.) flaviscutellata, L. (Psychodopygus) ayrozai and L. (Lutzomyia) longipalpis. Five species were new records in Ilha Grande: L. (Sciopemyia) microps, L. termitophila, L. firmatoi, L. rupicola and L. (P.) ayrozai. Higher species richness was found inside forest areas, although potential leishmaniases vectors were present in deforested areas, peridomiciles and inside houses. Lutzomyia (N.) intermedia and L. migonei were the most abundant species. Females of L. migonei showed a high rate (10.3%) of natural infection by Leishmania (Viannia) sp., probably Leishmania (V.) braziliensis. CONCLUSIONS: The detection of leishmaniases transmission and potential vectors in Ilha Grande is of public health concern, especially because tourists are frequently visiting the island. Besides reinforcing the epidemiological importance of L. (N.) intermedia in Rio de Janeiro State, the role of L. migonei in cutaneous leishmaniasis transmission is highlighted with its high rate of Leishmania natural infection. The finding of L. (L.) longipalpis confirmed the human autochthonous case of visceral leishmaniasis from the island. The presence of L. (N.) flaviscutellata in peridomestic areas is also an important finding, since the species is involved in the transmission of diffuse cutaneous leishmaniasis. Health education practices directed to the local community and tourists are important control actions that can be taken in Ilha Grande to reduce the burden of leishmaniases