Gumeni 2017 Abstract MITOEAGLE Barcelona
Impact of mitochondrial dynamics on the proteostasis network and longevity in Drosophila melanogaster
Event: MitoEAGLE Barcelona 2017
Mitochondria are essential organelles for cell function as they provide metabolites and energy . They are highly dynamic organelles that undergo continuous cycles of fusion and fission to mix and distribute their contents . These processes depend on the function of four conserved GTPases, the mitofusins Mfn1 and Mfn2 along with Optic Atrophy 1 (OPA1) which are implicated in fusion, as well as the dynamin-related protein 1 (Drp1) that is involved in fission. Beyond the organelle dynamics, the constant interaction with the ubiquitin-proteasome-system (UPS) has become an emerging aspect of healthy mitochondria . Mitochondrial dysfunction and impairment of UPS have been described as two hallmarks of ageing and they are implicated in many age-related diseases [3,4]. Herein, we present our analyses of the implication of mitochondrial dynamics in the molecular processes of ageing and their functional cross talk with the UPS and the autophagy-lysosome systems. Our in vivo studies in Drosophila have shown that impairment of fusion decreased muscle strength in flies and accelerated ageing. Alterations in mitochondrial dynamics impact on proteasome functionality, increased ROS levels and activated lysosomal cathepsins. We further found that loss of Opa1 in flies caused sterility, increased sensitivity to CO2 exposure and reduction of lifespan. Interestingly, loss of proteasome in Opa1 RNAi flies enhanced these toxic and deleterious effects, underlying the role of proteasome in alleviating the impact of loss of mitostasis. Our findings suggest the existence of extensive cross-talk and functional wiring between mitostatic and proteostatic modules; this cross talk is likely operating through a circuit of sensors that modulate proteolytic machineries in case of mitostasis disruption.
• Bioblast editor: Kandolf G
Labels: MiParea: mt-Structure;fission;fusion
- Gumeni S(1), Evangelakou Z(1), Tsakiri EN(1), Debattisti V(2), Papassideri IS(1), Scorrano L(2), Trougakos IP(1)
- Dept Cell Biology Biophysics, Fac Biol, National Kapodistrian Univ Athens, Greece
- Dulbecco-Telethon Inst, Venetian Inst Molecular Medicine Dept Biol, Univ Padua, Italy
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