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Grespi 2016 Abstract Mito Xmas Meeting Innsbruck

From Bioblast
MicroRNAs as modulators of mitochondrial remodeling and apoptosis.

Link:

Grespi F, Reffo L, Cagnin F, Lanfranchi G, Scorrano L (2016)

Event: Mito Xmas Meeting 2016 Innsbruck AT

Opa1 is a dynamin-related protein of the inner mitochondrial membrane mediating fusion and cristae remodeling, a key mechanism in apoptosis. Indeed, Opa1 is mutated in Autosomal Dominant Optic Atrophy (ADOA) a genetic disorder characterized by a high degree of phenotypic variability. Nevertheless, triggers determining the severity of the disease are still unknown. Intriguingly, emerging evidence highlight a link between mitochondrial fusion/fission and microRNAs, well-known epigenetic regulators. This suggests that miRNAs might participate in modulation of penetrance of diseases affecting mitochondrial shape. Accordingly, we performed an in silico screening to identify miRNAs putatively targeting the 3’UTR of Opa1. Our preliminary data demonstrate that specific miRNAs can directly modulate Opa1 levels, thus influencing mitochondrial shape and apoptosis. We identified specific cell death triggers inducing miRNAs expression, indicating that candidates are important at the beginning of the apoptotic cascade. For this reason, we hypothesize that the differential penetrance of ADOA is mediated by miRNAs and this feature can be exploited therapeutically. Indeed, our project is proposing an innovative mechanism of modulating ADOA penetrance that has never been investigated before. We believe that increasing levels of Opa1, even if mutated, by modulation of miRNAs by AntagomiRs, could ameliorate the phenotype of ADOA patients. In conclusion, our study could provide new potential therapeutic targets for a currently untreatable disease.


Labels: MiParea: mt-Structure;fission;fusion 

Stress:Cell death 





Event: B1, Oral 


Affiliations

Grespi F(1,2), Reffo L(1,2), Cagnin F(2,3), Lanfranchi G(2,3), Scorrano L(1,2)


  1. Venetian Inst Molecular Medicine, Padova, Italy
  2. Dept Biology, Univ Padova, Italy
  3. CRIBI Biotechnology Centre, Univ Padova, Italy