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Alan 2017 MiP2017
Coupling states ET  +
Has abstract [[Image:MITOEAGLE-logo.jpg|left|100px|link
[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MITOEAGLE]] Mitochondrial F<sub>1</sub>F<sub>O</sub> ATP synthase is the key enzyme of the oxidative phosphorylation apparatus, responsible for the production of up to 90% of the cellular ATP. The mammalian enzyme is composed of 17 structural subunits – two of the recently characterized ones (MLQ and DAPIT) are specific for higher eukaryotes. MLQ, also termed 6.8 kDa proteolipid (MP68), is nuclearly encoded protein with 58 amino acids, containing one putative membrane domain. The complete structure of MLQ, its stoichiometry within the enzyme, or its exact localization in the F<sub>O</sub> domain is as of yet unknown. To clarify the biological role of MLQ, we created a MLQ knock-out model in the HEK293 cells by the CRISPR/Cas9 technology. We demonstrate defective biogenesis of the fully assembled ATP synthase in the absence of MLQ. While mitochondrially encoded subunits F<sub>O</sub>-a and A6L are synthesized and assembled into the complex, MLQ is required for their stabilization in the holoenzyme. In its absence, F<sub>O</sub>-a and A6L dissociate and are degraded as confirmed by pulse chase experiments. As a result, at the steady state, incomplete enzyme lacking the proton channel formed by subunit F<sub>O</sub>-a is present in MLQ -/- mitochondria. At the functional level, we observed significantly reduced rates of ADP stimulated respiration in MLQ -/- cells, while the hydrolytic activity of the ATP synthase was preserved. Secondary to the ATP synthase deficiency we observed decreased mRNA and protein levels of the mitochondrially encoded subunits of cytochrome ''c'' oxidase (CIV). This led to the reduced levels of COX holoenzyme and decrease in ATP synthase independent state 3 (FCCP) respiration. We will discuss the molecular role of MLQ in F<sub>1</sub>F<sub>O</sub> ATP synthase assembly as well as the functional impact of MLQ KO on the cellular energetics. Moreover, we will report on progress of F<sub>O</sub>-a and A6L subunits degradation mechanism in MLQ KO cells.
its degradation mechanism in MLQ KO cells.  +
Has editor [[Kandolf G]]  +
Has title [[File:AlanL.jpg|left|90px|Alan Lukas]] Role of MLQ protein in the structure and function of mammalian F<sub>1</sub>F<sub>O</sub> ATP-synthase.  +
Instrument and method Oxygraph-2k  +
Mammal and model Human  +
MiP area Respiration  + , Genetic knockout;overexpression  +
Tissue and cell Kidney  +
Was published by MiPNetLab CZ Prague Houstek J +
Was submitted in year 2017  +
Was submitted to event MiP2017/MitoEAGLE Hradec Kralove CZ +
Was written by Alan L + , Ho DH + , Tauchmannova K + , Kaplanova V + , Houstek J + , Pecina P + , Mracek T +
Categories Abstracts
Modification date
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13:43:58, 3 November 2017  +
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