Gumeni 2018 MiP2018

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Disruption of mitochondria dynamics induces proteome instability and promotes ageing.

Link: MiP2018

Gumeni S, Evangelakou Z, Tsakiri EN, Scorrano L, Trougakos IP (2018)

Event: MiP2018


Mitochondria homeostasis is ensured by a complex network of mitochondria quality control modules and organelle dynamics. The ubiquitin-proteasome pathway (UPP) has been reported to have a critical role in maintaining mitochondrial health, by removing damaged proteins and affecting the mitochondrial proteome composition; thus regulating mitochondria dynamics. Yet, the mechanistic insights of mitostatic and proteostatic modules functional cross-talk remain elusive. We show herein that prolonged suppression of mitochondrial fusion, energetics or proteases in Drosophila tissues caused neuromusculatory defects and were either developmentally lethal and/or accelerated aging. Notably, downregulation of Opa1, a key regulator of inner mitochondrial membrane fusion, cristae remodeling and energetics, displayed gender dependent phenotypes with Drosophila males being more vulnerable. Disruption of mitostasis increased oxidative stress and proteome instability, causing activation of Nrf2 and Foxo to trigger the upregulation of mitostatic, as well as of cytoprotective antioxidant and proteostatic modules. Furthermore, while Nrf2 overexpression could not suppress the deleterious effects of loss-of mitostasis in flies’ tissues, these were alleviated by concomitant treatment with antioxidants or enhancement of autophagy. These findings can be translated to new therapeutic strategies for mitopathies.

Bioblast editor: Plangger M, Kandolf G

Labels: MiParea: mt-Medicine  Pathology: Aging;senescence 

Organism: Drosophila 


Gumeni S(1), Evangelakou Z(1), Tsakiri EN(1), Scorrano L(2), Trougakos IP(1)

  1. Dept Cell Biology Biophysics, Fac Biology, Univ Athens, Panepitimiopolis, Athens, Greece
  2. Dulbecco-Telethon Inst, Venetian Inst Molecular Medicine, Padova, Italy


Supported by Hellenic GSRT project BIOIMAGING-GR (MIS 5002755).