scholarly journals Reduced efficiency, but increased fat oxidation, in mitochondria from human skeletal muscle after 24-h ultraendurance exercise

2007 ◽  
Vol 102 (5) ◽  
pp. 1844-1849 ◽  
Author(s):  
Maria Fernström ◽  
Linda Bakkman ◽  
Michail Tonkonogi ◽  
Irina G. Shabalina ◽  
Zinaida Rozhdestvenskaya ◽  
...  
Keyword(s):  
Electron Transport ◽  
Electron Transport Chain ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Oxygen Demand ◽  
Atp Synthesis ◽  
Whole Body ◽  
Palmitoyl Carnitine ◽  
Transport Chain ◽  
Mitochondrial Efficiency

The hypothesis that ultraendurance exercise influences muscle mitochondrial function has been investigated. Athletes in ultraendurance performance performed running, kayaking, and cycling at 60% of their peak O2 consumption for 24 h. Muscle biopsies were taken preexercise (Pre-Ex), postexercise (Post-Ex), and after 28 h of recovery (Rec). Respiration was analyzed in isolated mitochondria during state 3 (coupled to ATP synthesis) and state 4 (noncoupled respiration), with fatty acids alone [palmitoyl carnitine (PC)] or together with pyruvate (Pyr). Electron transport chain activity was measured with NADH in permeabilized mitochondria. State 3 respiration with PC increased Post-Ex by 39 and 41% ( P < 0.05) when related to mitochondrial protein and to electron transport chain activity, respectively. State 3 respiration with Pyr was not changed ( P > 0.05). State 4 respiration with PC increased Post-Ex but was lower than Pre-Ex at Rec ( P < 0.05 vs. Pre-Ex). Mitochondrial efficiency [amount of added ADP divided by oxygen consumed during state 3 (P/O ratio)] decreased Post-Ex by 9 and 6% ( P < 0.05) with PC and PC + Pyr, respectively. P/O ratio remained reduced at Rec. Muscle uncoupling protein 3, measured with Western blotting, was not changed Post-Ex but tended to decrease at Rec ( P = 0.07 vs. Pre-Ex). In conclusion, extreme endurance exercise decreases mitochondrial efficiency. This will increase oxygen demand and may partly explain the observed elevation in whole body oxygen consumption during standardized exercise (+13%). The increased mitochondrial capacity for PC oxidation indicates plasticity in substrate oxidation at the mitochondrial level, which may be of advantage during prolonged exercise.

The efficiency and plasticity of mitochondrial energy transduction

2005 ◽  
Vol 33 (5) ◽  
pp. 897-904 ◽  
Author(s):  
M.D. Brand
Keyword(s):  
Electron Transport ◽  
Atp Synthase ◽  
Electron Transport Chain ◽  
Uncoupling Protein ◽  
Coupling Efficiency ◽  
Energy Transduction ◽  
Proton Pumping ◽  
Complex Iii ◽  
Proton Pumps ◽  
Transport Chain

Since it was first realized that biological energy transduction involves oxygen and ATP, opinions about the amount of ATP made per oxygen consumed have continually evolved. The coupling efficiency is crucial because it constrains mechanistic models of the electron-transport chain and ATP synthase, and underpins the physiology and ecology of how organisms prosper in a thermodynamically hostile environment. Mechanistically, we have a good model of proton pumping by complex III of the electron-transport chain and a reasonable understanding of complex IV and the ATP synthase, but remain ignorant about complex I. Energy transduction is plastic: coupling efficiency can vary. Whether this occurs physiologically by molecular slipping in the proton pumps remains controversial. However, the membrane clearly leaks protons, decreasing the energy funnelled into ATP synthesis. Up to 20% of the basal metabolic rate may be used to drive this basal leak. In addition, UCP1 (uncoupling protein 1) is used in specialized tissues to uncouple oxidative phosphorylation, causing adaptive thermogenesis. Other UCPs can also uncouple, but are tightly regulated; they may function to decrease coupling efficiency and so attenuate mitochondrial radical production. UCPs may also integrate inputs from different fuels in pancreatic β-cells and modulate insulin secretion. They are exciting potential targets for treatment of obesity, cachexia, aging and diabetes.

THE EFFECT OF LETHAL DOSES OF X-IRRADIATION ON THE ENZYMATIC ACTIVITY OF MITOCHONDRIAL CYTOCHROME c

1966 ◽  
Vol 44 (4) ◽  
pp. 433-448 ◽  
Author(s):  
J. F. Scaife
Keyword(s):  
Electron Transport ◽  
Cytochrome C ◽  
Electron Transport Chain ◽  
Reductase Activity ◽  
Ehrlich Ascites Carcinoma ◽  
Whole Body ◽  
Triphenyltetrazolium Chloride ◽  
Transport Chain ◽  
Ehrlich Ascites ◽  
X Irradiation

The coupling of the tetrazolium salts triphenyltetrazolium chloride and nitro-blue tetrazolium to the electron transport chain in mitochondria of thymus, spleen, liver, kidney, and Ehrlich ascites carcinoma cells has been studied with several substrates. In experiments on succinate–triphenyltetrazolium chloride reductase activity it has been possible to demonstrate a radiation lesion in the electron transport chain of mitochondria from thymus and spleen, but not in those from other tissues. This lesion is evident 4 hours after 25 rad of whole-body irradiation, or earlier with higher doses. It is not prevented by the prior administration of aminoethylisothiouronium bromide, serotonin, vitamin K1, or vitamin E, but is reduced by anoxic conditions.Lower levels of cytochrome c are found in irradiated mitochondria isolated from thymus, and the radiation lesion is believed to be produced by loosening the binding of cytochrome c to the mitochondrial membrane after X-irradiation. Decreased levels of ATP occur in thymus, spleen, and ascites cells following irradiation.

scholarly journals Electron transport chain biogenesis activated by a JNK-insulin-Myc relay primes mitochondrial inheritance in Drosophila

2019 ◽  
Author(s):  
Zong-Heng Wang ◽  
Yi Liu ◽  
Vijender Chaitankar ◽  
Mehdi Pirooznia ◽  
Hong Xu
Keyword(s):  
Electron Transport ◽  
Mitochondrial Respiration ◽  
Electron Transport Chain ◽  
Protein Import ◽  
Mitochondrial Protein ◽  
Mtdna Copy Number ◽  
Mtdna Mutation ◽  
Cellular Mechanisms ◽  
Transport Chain ◽  
Mtdna Replication

SUMMARYOogenesis features an enormous increase in mitochondrial mass and mtDNA copy number, which are required to furnish mature eggs with adequate mitochondria and to curb the transmission of deleterious mtDNA variants. Quiescent in dividing germ cells, mtDNA replication initiates upon oocyte determination in the Drosophila ovary, which necessitates active mitochondrial respiration. However, the underlying mechanism for this dynamic regulation remains unclear. Here, we show that an feedforward insulin-Myc loop promotes mitochondrial respiration and biogenesis by boosting the expression of electron transport chain subunits and factors essential for mtDNA replication and expression, and mitochondrial protein import. We further reveal that transient activation of JNK enhances the expression of insulin receptor and initiates the insulin-Myc signaling loop. Importantly, this signaling relay ensures sufficient mtDNA in eggs and limits the transmission of a deleterious mtDNA mutation. Our study demonstrates cellular mechanisms that couple mitochondrial biogenesis and inheritance with oocyte development.

scholarly journals Terminal Respiratory Oxidases: A Targetables Vulnerability of Mycobacterial Bioenergetics?

2020 ◽  
Vol 10 ◽  
Author(s):  
Sapna Bajeli ◽  
Navin Baid ◽  
Manjot Kaur ◽  
Ganesh P. Pawar ◽  
Vinod D. Chaudhari ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Electron Transport ◽  
Molecular Oxygen ◽  
Electron Transport Chain ◽  
Drug Targets ◽  
Atp Synthesis ◽  
Terminal Oxidase ◽  
Terminal Oxidases ◽  
Transport Chain ◽  
Synthase Inhibitor

Recently, ATP synthase inhibitor Bedaquiline was approved for the treatment of multi-drug resistant tuberculosis emphasizing the importance of oxidative phosphorylation for the survival of mycobacteria. ATP synthesis is primarily dependent on the generation of proton motive force through the electron transport chain in mycobacteria. The mycobacterial electron transport chain utilizes two terminal oxidases for the reduction of oxygen, namely the bc1-aa3 supercomplex and the cytochrome bd oxidase. The bc1-aa3 supercomplex is an energy-efficient terminal oxidase that pumps out four vectoral protons, besides consuming four scalar protons during the transfer of electrons from menaquinone to molecular oxygen. In the past few years, several inhibitors of bc1-aa3 supercomplex have been developed, out of which, Q203 belonging to the class of imidazopyridine, has moved to clinical trials. Recently, the crystal structure of the mycobacterial cytochrome bc1-aa3 supercomplex was solved, providing details of the route of transfer of electrons from menaquinone to molecular oxygen. Besides providing insights into the molecular functioning, crystal structure is aiding in the targeted drug development. On the other hand, the second respiratory terminal oxidase of the mycobacterial respiratory chain, cytochrome bd oxidase, does not pump out the vectoral protons and is energetically less efficient. However, it can detoxify the reactive oxygen species and facilitate mycobacterial survival during a multitude of stresses. Quinolone derivatives (CK-2-63) and quinone derivative (Aurachin D) inhibit cytochrome bd oxidase. Notably, ablation of both the two terminal oxidases simultaneously through genetic methods or pharmacological inhibition leads to the rapid death of the mycobacterial cells. Thus, terminal oxidases have emerged as important drug targets. In this review, we have described the current understanding of the functioning of these two oxidases, their physiological relevance to mycobacteria, and their inhibitors. Besides these, we also describe the alternative terminal complexes that are used by mycobacteria to maintain energized membrane during hypoxia and anaerobic conditions.

scholarly journals Some living beings speak up against ‘electron transport chain – chemiosmosis – rotary ATP synthesis’ bioenergetics model

2021 ◽  
Author(s):  
Kelath Murali Manoj
Keyword(s):  
Electron Transport ◽  
Electron Transport Chain ◽  
Molecular Motor ◽  
Atp Synthesis ◽  
Malarial Parasite ◽  
Proton Pumps ◽  
Buchnera Aphidicola ◽  
Transport Chain ◽  
Parasite Plasmodium ◽  
Speak Up

Since 2017, I have argued that affinity/contact-based electron transport chain (ETC) and chemiosmotic rotary ATP synthesis (CRAS) explanation fail to reason the workability or evolution of cellular bioenergetics. Cyanobacteria (Prochlorococcus) can both respire and photosynthesize. In these systems, the aqueous milieu of &lt;0.1 femtoliter (pH 8) cannot afford any free protons to build ‘pmf’’, thereby negating chemiosmosis. The anti-parallel ETCs (NADH→H2O in respiration and H2O→NADH in photosynthesis) would lead to futile cycles, owing to the commonality of cytochromes b6f and c1. Aphids of genus Acyrthosiphon use the inbuilt carotenoid pigments to reduce NAD and synthesize ATP, without elaborate setups like Z-scheme. The classical perceptions deem archaeans to have a unique bioenergetic history, distinct from bacteria/eukarya. Although it is known that archaea lack FoF1ATP(synth)ase, the ‘molecular motor’ is otherwise believed to be conserved in bacterial/eukaryotic systems. However, the genes of Complex V are not clubbed/linked in proteobacterial Rickettsia prowazekii. Several parasitic and a free-living alveolate Tetrahymena thermophila lack essential proteins of Fo module. Complex V is completely absent in the blood-stage malarial parasite (Plasmodium berghei) and Buchnera aphidicola (a proteobacterium, endosymbiont of cedar bark aphid). Monocercomonoides (a flagellate oxymonad rodent-gut symbiont) and human erythrocytes generate ATP without mitochondria! The recently discovered cnidarian parasite Henneguya salminicola does not have respiratory Complexes I, III &amp; IV, the purported classical proton pumps. While the ETC-CRAS model is incompatible with these facts, the newly available murburn alternative accommodates them. The principles of scientific pursuits and Ockham’s razor decide in favor of the murburn model of bioenergetics.

scholarly journals Cyclophilin D, Somehow a Master Regulator of Mitochondrial Function

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 176 ◽  
Author(s):  
George A. Porter ◽  
Gisela Beutner
Keyword(s):  
Electron Transport ◽  
Mitochondrial Function ◽  
Electron Transport Chain ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mitochondrial Protein ◽  
Cyclophilin D ◽  
Master Regulator ◽  
Transport Chain

Cyclophilin D (CyPD) is an important mitochondrial chaperone protein whose mechanism of action remains a mystery. It is well known for regulating mitochondrial function and coupling of the electron transport chain and ATP synthesis by controlling the mitochondrial permeability transition pore (PTP), but more recent evidence suggests that it may regulate electron transport chain activity. Given its identification as a peptidyl-prolyl, cis-trans isomerase (PPIase), CyPD, is thought to be involved in mitochondrial protein folding, but very few reports demonstrate the presence of this activity. By contrast, CyPD may also perform a scaffolding function, as it binds to a number of important proteins in the mitochondrial matrix and inner mitochondrial membrane. From a clinical perspective, inhibiting CyPD to inhibit PTP opening protects against ischemia–reperfusion injury, making modulation of CyPD activity a potentially important therapeutic goal, but the lack of knowledge about the mechanisms of CyPD’s actions remains problematic for such therapies. Thus, the important yet enigmatic nature of CyPD somehow makes it a master regulator, yet a troublemaker, for mitochondrial function.

scholarly journals Aerobic Respiration: Criticism of the Proton-centric Explanation Involving Rotary Adenosine Triphosphate Synthesis, Chemiosmosis Principle, Proton Pumps and Electron Transport Chain

2018 ◽  
Vol 11 ◽  
pp. 117862641881844 ◽  
Author(s):  
Kelath Murali Manoj
Keyword(s):  
Electron Transport ◽  
Adenosine Triphosphate ◽  
Electron Transport Chain ◽  
Atp Synthesis ◽  
Cellular Respiration ◽  
Aerobic Respiration ◽  
Proton Pumps ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Transport Chain ◽  
Interactive Dynamics

The acclaimed explanation for mitochondrial oxidative phosphorylation (mOxPhos, or cellular respiration) is a deterministic proton-centric scheme involving four components: Rotary adenosine triphosphate (ATP)-synthesis, Chemiosmosis principle, Proton pumps, and Electron transport chain (abbreviated as RCPE hypothesis). Within this write-up, the RCPE scheme is critically analyzed with respect to mitochondrial architecture, proteins’ distribution, structure-function correlations and their interactive dynamics, overall reaction chemistry, kinetics, thermodynamics, evolutionary logic, and so on. It is found that the RCPE proposal fails to explain key physiological aspects of mOxPhos in several specific issues and also in holistic perspectives. Therefore, it is imperative to look for new explanations for mOxPhos.

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