ATP synthase
Without ATP hydrolysis, this was 1 15 · 10-3, so A « B conversion has been increased by a factor of 108 ATP synthase is the ATP factory which synthesizes most of ATP in organisms ATP synthase Bacteria ATP synthase Mitochondria ATP synthase Chloroplast
ATP Synthase and the Actions of Inhibitors Utilized To Study
lation, suggesting ATP synthase as a molecular target for antiobesity drugs (16) Finally, the inhibition of ATP syn-thase has been suggested for an antiangiogenic therapeutic strategy to block tumor angiogenesis (17, 59, 269–271, 422) Here, the reaction of ATP synthase inhibitors with the non-mitochondrial ATP synthase of endothelial cells
Macromolecular organization of ATP synthase and complex I in
complexes into regions that are either rich in ATP synthase or in complex I, and the extended rows of ATP synthase dimers on the cristae edges has important implications for ATP synthesis in mitochondria Results and Discussion Cryo-ET of Whole Mitochondria Cryo-ET is the method of choice for visualizing the three-dimensional organization of
ATP Synthase Subunit a Supports Permeability Transition in
Niedzwiecka et al : ATP Synthase Subunit a Alters PTP Conductance in Yeast cells In OM45-GFP cells, in which Tim11 is present, these mutations increased the fraction of swollen mitochondria by up to 85 vs 60 in the wild type, although the time required for calcium release doubled Conclusion: ATP synthase subunit e is essential in the S
ab109716 – ATP Synthase Microplate Assay Kit Specific Activity
The mammalian ATP synthase is composed of 17 subunits Five of the subunits make up the easily detached F1 domain The remainder subunits are part of two stalk domains and the proton pumping F0 domain Two of the F0 subunits are encoded on mitochondrial (mt) DNA while all other subunits of the ATP synthase complex are nuclear encoded
ab109714 – ATP Synthase Microplate Assay Kit Enzyme Activity
May 08, 2018 · The ATP synthase complex (EC 3 6 3 14), also called Complex V or F 1 F 0 ATPase, is responsible for ATP production in the oxidative phosphorylation process and can work in reverse as a proton
ATP SYNTHASE — A MARVELLOUS ROTARY ENGINE OF THE CELL
ATP synthase as a complex of two motors — an ATP-driven F 1 motor and a proton-driven F o motor They are connected by a common rotary shaft and their genuine directions of rotation are opposite
The metabolite α-ketoglutarate extends lifespan by inhibiting
of steady-state inhibition kinetics of ATP synthase by a-KG (produced by insituhydrolysisofoctyla-KG) [S]isthesubstrate(ADP)concentration,and V is the initial velocity of ATP synthesis in the presence of 200mM octanol
A ATP synthase, chloroplast - ResearchGate
Keywords: chloroplast/ATP synthase/F0 subunit/plastid coded ficiently to allow comparison to bemadewithbacterial or mito- chondrial subunitsbutthegeneforthis subunitis located in the
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LETTER
doi:10.1038/nature13264The metabolitea-ketoglutarate extends lifespan by
inhibiting ATP synthase and TORRandallM.Chin
1 ,XudongFu 2 ,MelodyY.Pai 1 *,LaurentVergnes 3 *,HeejunHwang 2 *,GangDeng 4 ,SimonDiep 2 ,BrettLomenick 2Vijaykumar S. Meli
5 , Gabriela C. Monsalve 5 , Eileen Hu 2 , Stephen A. Whelan 6 , Jennifer X. Wang 7 , Gwanghyun Jung 2GregoryM.Solis
8 ,FarbodFazlollahi 9 ,ChitradaKaweeteerawat 10 ,AustinQuach 2 , MahtaNili 11 ,AbbyS.Krall 2 , HilaryA.Godwin 10,Helena R. Chang
6 , Kym F. Faull 9 , Feng Guo 5 , Meisheng Jiang 2 , Sunia A. Trauger 7 , Alan Saghatelian 12 , Daniel Braas 2,13Heather R. Christofk
2,13 , Catherine F. Clarke 1,4 , Michael A. Teitell 1,11 , Michael Petrascheck 8 , Karen Reue 1,3 , Michael E. Jung 1,4Alison R. Frand
5 & Jing Huang 1,2 Metabolism and ageing are intimately linked. Compared withad libitum 1,2 .Sim- ilar conditions of nutrient limitation and genetic or pharmacological benefits 3,4 . Recently, several metabolites have been identified that modulateageing 5,6atricarboxylicacidcycleintermediate,extendsthelifespanofadultCaenorhabditis elegans. ATP synthase subunitbis identified as a
novel binding protein ofa-KG using a small-molecule target iden- tification strategy termed drug affinity responsive target stability (DARTS) 7 chondrial electron transport chain, is the main cellular energy- 8,9 Although complete loss of mitochondrial function is detrimental, partial suppression of the electron transport chain has been shown toextendC.eleganslifespan
10Ö13
. Weshowthata-KGinhibitsATP synthase and, similar to ATP synthase knockdown, inhibition by a-KG leads to reduced ATP content, decreased oxygen consump- tion, and increased autophagy in bothC. elegansand mammalian
ATP synthase subunitband is dependent on target of rapamycin (TOR)downstream.Endogenousa -KGlevelsareincreasedonstar- vation anda-KG does not extend the lifespan of dietary-restricted gevity by dietary restriction. Our analyses uncover new molecular linksbetween a common metabolite,a universal cellularenergy gen- thus suggesting new strategies for the prevention and treatment of ageing and age-related diseases. We discovered that the tricarboxylic acid (TCA) cycle intermediate a-KG (but not isocitrate or citrate) delays ageing and extends the life- dative decarboxylation catalysed by isocitrate dehydrogenase (IDH). worms in a concentration-dependent manner, with 8mMa-KG pro- increaseina-KGconcentrationinworms on 8mMa-KGplatescom- as the decline in rapid, coordinated body movement (Supplementary Videos 1 and 2).a-KGsupplementation in the adult stage is sufficient for longevity (Extended Data Fig. 1c). shown to extend worm lifespan14 , but the lifespan increase by a-KG is not due to altered bacterial proliferation or metabolism (Fig. 1d, e and less favourable (Extended Data Fig. 1e, f), and there was no significant change in food intake, pharyngeal pumping, foraging behaviour, body size or brood size in the presence ofa-KG (Extended Data Fig. 1eÖh; data not shown). bya-KG Increasinga-KG levels byogdh-1RNA interference (RNAi) (Extended Data Fig. 1b) also extends worm lifespan (Fig. 1f and Supplementary Notes), consistent with a direct effect ofa-KG on longevity indepen- dent of bacterial food. To investigate the molecular mechanism(s) of longevity bya-KG, 7 .As we proposed that key target(s) ofa-KG are likely to be conserved and ubiquitously expressed, we used a human cell line (Jurkat) that is easy among the most abundant and enriched proteins present in thea-KG- corroborated fortheC.elegansorthologueATP-2(ExtendedDataFig.2a). a-KG inhibits the activity of complex V, but not complex IV, frombovineheartmitochondria(Fig.2candExtendedDataFig.2b;datanot*These authors contributed equally to this work.
1Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095, USA.
2 Department of Molecular and Medical Pharmacology, University of California Los Angeles, LosAngeles, California 90095, USA.
3Department of Human Genetics, University of California Los Angeles, Los Angeles, California 90095, USA.4
Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, California 90095, USA. 5Department of Biological Chemistry, University of California Los Angeles, Los Angeles, California 90095, USA.
6Department of Surgery,
University of California Los Angeles, Los Angeles, California 90095, USA. 7Small Molecule Mass Spectrometry Facility,FAS Division of Science, Harvard University, Cambridge, Massachusetts 02138, USA.
8 Departmentof ChemicalPhysiology,The ScrippsResearch Institute,La Jolla, California 92037, USA. 9 Pasarow Mass SpectrometryLaboratory,Department of Psychiatryand Biobehavioral Sciencesand 10Angeles,LosAngeles,California90095,USA.
11 12DepartmentofChemistryand
Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. 13 UCLA Metabolomics Center, University of California Los Angeles, Los Angeles, California 90095, USA.19 JUNE 2014 | VOL 510 | NATURE | 397
Macmillan Publishers Limited. All rights reserved©2014 (Fig.2d;datanotshown) and inlive nematodes(Fig.2e), asevidenced by reduced ATP levels. Concomitantly, oxygenconsumption rates are lowered (Fig. 2f, g), similar to withatp-2knockdown (Extended Data Fig. 2c). Specific inhibition of complex V"but not the other electron transport chain (ETC) complexes"bya-KG is further confirmed by respiratory control analysis 15 (Fig. 2h and Extended Data Fig. 2d...h). To understand the mechanism of inhibition bya-KG, we studied theenzymeinhibitionkineticsofATPsynthase.a-KG(releasedfromoctyla-KG) decreases both the effective velocity of the enzyme-catalysed
reaction at an infinite concentration of the substrate (V max ) and theMichaelisconstant (K
m ) ofATPsynthase, indicative ofuncompetitive inhibition (Fig. 2i and Supplementary Notes). To determine the significance of ATP-2 to the longevity bya-KG, previously 13 ,atp-2RNAi animals live longer than control RNAi ani-02468101214161820171819202122
010Per cent alive
Day of adulthood
20 30 010Day of adulthood
20 300 10
Day of adulthood
20 300 10
Day of adulthoodControl, vehicle
ogdh-1RNAi, vehicle
ogdh-1 RNAi, -KGControl, -KG20 300
20406080100
Per cent alive
020406080100
Per cent alive
020406080100
Per cent alive
020406080100
AmpicillinVehicle
Live OP50
Dead OP50
-KGVehicle
-KGVehicle
-KG -KG (mM)VehicleCitrate
Isocitrate
Succinate
Pyruvate
Mean lifespan
(days of adulthood) -KG b a d e f c OH OO O HO Figure 1|a-KGextendstheadultlifespanofC.elegans.a,a-KGextendsthe lifespan of adult worms in the metabolite longevity screen. All metabolites were givenata concentrationof8mM.b,Structureofa-KG.c,Dose...response fed bacteria that have been ampicillin arrested, mean lifespan (days of adulthood) with vehicle treatment(m veh )519.4 (n580 animals tested),m a-KG525.1 (n591),P,0.0001 (log-rank test) (d); orc-irradiation-killed,
m veh519.0 (n588),m
a-KG523.0 (n546),P,0.0001 (log-rank test) (e).
RNAi worms,m
veh521.2 (n598),m
a-KG521.1 (n5100),P50.65 (log-
rank test). a100 1,000 0 1:1,000 Pronase
250130
95
72
55
36
28
17 11 0 0 b c
Pronase 1:100
0 50 100 0 200
IB: ATP5B
IB: GAPDH
IB: ATP5O 50
6030
40 50
4050
40 IB: PHD-2
d e g h f iRotenone
Succinate State 4o
8768
48
28
8 -11