SfRBM 2017 173 quantitatively measure mitochondrial network features in cells treated with E2 or the selective estrogen receptor-α and β modulators (SERMs) propylpyrazole triol (PPT) and diarylpropionitrile (DPN), respectively. 48h treatment of mouse C2C12 myoblasts with various concentrations of either E2 or DPN, but not PPT, significantly modified mitochondrial network morphology. Both E2 and DPN approximately doubled the number of mitochondrial networks as well as the number of branches per network, while PPT had no effect on these parameters. Similarly, both E2 and DPN significantly increased the mitochondrial footprint, a measure of mitochondrial abundance, while PPT failed to modulate this feature. These data indicate that ER- β agonists strongly promote mitochondrial fusion. Thus, these observations provide initial quantitative evidence of beneficial actions of SERMs such as DPN as a pharmacological tool for targeting mitochondrial fusion in pathological conditions characterized by deficient mitochondrial network formation, such as certain neurodegenerative diseases and cancers. DOI: 10.1016/j.freeradbiomed.2017.10.269 257 Redox Paradox: The Contribution of Reactive Oxygen Species (ROS) in the Proliferation and Differentiation of Trypanosoma cruzi Natalia Nogueira 1 , Francis Saraiva 1 , Jessica Oliveira 1 , Gustavo Laranja 1 , Elmo Almeida-Amaral 2 , Georgia Atella 3 , Marcus Oliveira 3 , and Marcia Paes 1 1 University of State of Rio de Janeiro -UERJ, Brazil 2 IOC - FIOCRUZ, Brazil 3 Federal University of Rio de Janeiro - UFRJ, Brazil Trypanosoma cruzi is a protozoan that causes Chagas disease or American trypanosomiasis. The parasite has a heteroxenic biological cycle developing between a vertebrate host (mammal) and an invertebrate (insect vector). The first environment encountered by T. cruzi after the blood meal is the midgut of the insect, where large amounts of hemoglobin are degraded resulting in the release of huge concentrations of heme, a molecule known to increase the formation of ROS. Heme induces T. cruzi proliferation, and this phenomenon is accompanied by a marked time and concentration dependent increase in ROS formation and the modulation of epimastigotes mitochondrial physiology in an effort to increase ROS as a metabolic mechanism to maintain epimastigote survival and proliferation. Conversely, the antioxidants reverse the heme-induced ROS and dramatically impair epimastigotes proliferation. Following the cycle, when these forms are taken into the hindgut of the triatomine they return to the non-replicative, infective form, the metacyclic trypomastigotes. During the metacyclogenesis, antioxidants induce a significant increment of trypomastigotes. These data gives us the idea of a “shift” between proliferation to differentiation according to the influence of the redox status. Surprisingly, when metacyclic trypomastigotes are released into the insect feces the infection is again favored by ROS since inhibitors of Nox and antioxidants greatly decrease macrophage infection. Moreover, while the parasite needs oxidants for its proliferation inside the vector, the opposite occurs during its development inside the vertebrate host. H 2 O 2 diminishes amastigotes proliferation and increases the trypomastigote differentiation into amastigotes. Taken together, our data reveal a redox paradox in which ROS plays antagonistic roles along Trypanosoma cruzi life cycle demonstrating a high capacity to adapt to its habitats. DOI: 10.1016/j.freeradbiomed.2017.10.270 258 Poldip2 is an Oxygen-sensitive Mitochondrial Protein that Controls Oxidative/glycolytic Metabolism Balance and Proteasome Activity Felipe Paredes 1 , Holly Williams 1 , and Alejandra San Martin 1 1 Emory University, USA The polymerase delta interacting protein 2 (Poldip2) is a nuclear-encoded mitochondrial protein of unknown function. We recently reported that Poldip2 is repressed under hypoxia and that its deficiency results in repressed mitochondrial function and increased glycolytic activity. However, the mechanisms responsible for this metabolic reprograming and its consequences are unknown. In this