Samardzic 2015 Abstract MiPschool London 2015

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In vitro and in vivo study of the mitochondria shaping protein Opa1 in cancer.

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Samardzic D, Danial N, Scorrano L (2015)

Event: MiPschool London 2015

Mitochondria are key organelles that amplify apoptosis [1]. Deregulation of apoptosis is a typical hallmark of cancer [2]. Changes in the shape and in the ultrastructure of the organele contribute to the progression of apoptosis. They are controlled by a family of proteins that include, amongst others, the inner membrane GTPase Opa1 [3]. 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 acquisition and maintenance of the cancer phenotype, both in cellular (diffuse large B cell lymphoma - DLBCL), and animal lymphoma models (Emu-myc / Opa1 transgenic animals). Western blot analysis, followed by densitometry quantification, revealed that 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. Pathology / histopathology analysis of mice revealed that Eμ-myc / Opa1tg mice develop a stronger tumorigenic phenotype compared to Eμ-myc mice over time, and KM survival analysis demonstrated that Eμ-myc / Opa1tg mice die sooner then Eμ-myc mice.

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 indicate a role for Opa1 in DLBCL features, and tumor progression in vivo.


Labels: MiParea: mt-Structure;fission;fusion  Pathology: Cancer 

Organism: Mouse  Tissue;cell: Other cell lines 





Affiliations

1-Venetian Inst Mol Med (VIMM), Padova, Italy. - dijana.samardzic@gmail.com

2-Dept Biol, Univ Padova, Italy

3-Dept Cancer Biol, Dana – Farber Cancer Inst, Boston, MA, USA

References

  1. Thompson CB (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267:1456-62.
  2. Wasilewski M, Scorrano L (2009) The changing shape of mitochondrial apoptosis. Trends Enocrinol Metab 20:287-94.
  3. Cipolat, S, Rudka, T, Hartmann D, Costa V, Serneels L, Craessaerts K, Metzger K, Frezza C, Annaert W, D'Adamio L, Derks C, Dejaegere T, Pellegrini L, D'Hooge R, Scorrano L, and De Strooper B (2006) Cell 126:163-75.