Trifunovic 2019 MiP2019

From Bioblast
Aleksandra Trifunovic
Keeping mitochondria in shape.

Link: MiP2019

Trifunovic A (2019)

Event: MiP2019


Mitochondria are the central hub for metabolism providing the majority of cellular ATP yield through the action of respiratory chain coupled to an A prevailing driving force for all the ATP synthesis in our cells enters the oxidative phosphorylation (OXPHOS) system through the Complex I (CI), which is the largest enzyme of respiratory chain and the most commonly affected in mitochondrial diseases. Mammalian CI consists of 44 different subunits organized in a modular, L-shaped, membrane-rooted structure. Although the principles of stepwise CI biogenesis have been recently described in details, the regulation of its turnover, remodelling and stability remains enigmatic. The membrane-embedded components of OXPHOS complexes seem to be actively removed by mAAA and iAAA proteases. However the exact players involved in the turnover of CI periphery arm as well as mechanisms that allow their selective clearance remain unknown.

Our latest result show that mitochondrial matrix protease, CLPXP is required for a constant turnover of N-module part of the CI peripheral arm that occurs at the higher rate and independently of the rest of CI. Remarkably, a loss of CLPP protease stabilizes the fully assembled CI in a number of models, indicating that mitochondrial quality control pathways may exacerbate the pathological consequences of respiratory chain deficiency, particularly in instances associated with structural instability of OXHOS complexes. Our findings suggest that CLPXP protease plays an unforeseen role in a regulation of CI stability upon respiratory chain dysfunction and identifies CLPP as an exciting new target for therapy of mitochondrial diseases.

β€’ Bioblast editor: Plangger M, Tindle-Solomon L

Labels: MiParea: mt-Membrane 

Enzyme: Complex I 


Cologne Excellence Cluster Cellular Stress Responses Aging-Associated Diseases (CECAD), Inst Mitochondrial Diseases Aging, Medical Fac, Univ Cologne, Germany
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