Samardzic 2016 Abstract Mito Xmas Meeting Innsbruck

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Increased Opa1 levels aggravate B cell lymphoma.

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Samardzic D, Danial N, Scorrano L (2016)

Event: Mito Xmas Meeting 2016 Innsbruck AT

Mitochondria are key organelles that amplify apoptosis. Deregulation of apoptosis is a typical hallmark of cancer. Changes in the shape and in the ultrastructure of the organelle contribute to the progression of apoptosis. They are controlled by a family of proteins that include, amongst others, the inner membrane GTPase Opa1. When cells express mutated inactive Opa1 they are more susceptible to apoptosis, whereas cellular and animal models of Opa1 overexpression display a resistance to apoptosis. We aimed to elucidate what is the role of Opa1 in the acquisition and maintenance of the cancer phenotype, in cellular (DLBCL), and animal lymphoma models (Eμ-myc / Opa1tg animals). BCR vs. OxPhos DLBCL cell subsets differ in the overall ratio between long and short Opa1 forms. The relative balance between these forms is necessary for Opa1 function, and here we show that the balance between these forms is maintained in the OxPhos subset, whereas in the BCR subset short forms accumulate. Immunological, histopathological and survival analysis of mice revealed that Eμ-myc / Opa1tg mice have a shorter life span and develop a stronger tumorigenic phenotype compared to Eμ-myc mice over time. Here we present evidence that mitochondrial morphology, metabolism, and ultrastructure are different between the BCR and the OxPhos DLBCL subsets that display different levels of Opa1. We also show evidence that overexpression of Opa1 is contributing to the development of cancer in Eμ-Myc transgenic animals. Our data indicates a role for Opa1 in DLBCL features, and tumor progression in vivo.


Labels: MiParea: mt-Structure;fission;fusion  Pathology: Cancer  Stress:Cell death 





Event: A1, Oral 


Affiliations

Samardzic D(1,2), Danial N(3), Scorrano L(1,2)
  1. Venetian Inst Molecular Medicine (VIMM), Padova, Italy
  2. Dept Biology, Univ Padova, Italy
  3. Dept Cancer Biol, Dana – Farber Cancer Inst, Boston, MA, USA