scholarly journals Molecular and Supramolecular Structure of the Mitochondrial Oxidative Phosphorylation System: Implications for Pathology

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 242
Author(s):  
Salvatore Nesci ◽  
Fabiana Trombetti ◽  
Alessandra Pagliarani ◽  
Vittoria Ventrella ◽  
Cristina Algieri ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Mitochondrial Permeability Transition ◽  
Ros Generation ◽  
Protonmotive Force ◽  
Mitochondrial Oxidative Phosphorylation ◽  
F1fo Atp Synthase ◽  
Functional Changes ◽  
Age Related ◽  
Mitochondrial Functions

Under aerobic conditions, mitochondrial oxidative phosphorylation (OXPHOS) converts the energy released by nutrient oxidation into ATP, the currency of living organisms. The whole biochemical machinery is hosted by the inner mitochondrial membrane (mtIM) where the protonmotive force built by respiratory complexes, dynamically assembled as super-complexes, allows the F1FO-ATP synthase to make ATP from ADP + Pi. Recently mitochondria emerged not only as cell powerhouses, but also as signaling hubs by way of reactive oxygen species (ROS) production. However, when ROS removal systems and/or OXPHOS constituents are defective, the physiological ROS generation can cause ROS imbalance and oxidative stress, which in turn damages cell components. Moreover, the morphology of mitochondria rules cell fate and the formation of the mitochondrial permeability transition pore in the mtIM, which, most likely with the F1FO-ATP synthase contribution, permeabilizes mitochondria and leads to cell death. As the multiple mitochondrial functions are mutually interconnected, changes in protein composition by mutations or in supercomplex assembly and/or in membrane structures often generate a dysfunctional cascade and lead to life-incompatible diseases or severe syndromes. The known structural/functional changes in mitochondrial proteins and structures, which impact mitochondrial bioenergetics because of an impaired or defective energy transduction system, here reviewed, constitute the main biochemical damage in a variety of genetic and age-related diseases.

scholarly journals The ATP Synthase Deficiency in Human Diseases

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 325
Author(s):  
Chiara Galber ◽  
Stefania Carissimi ◽  
Alessandra Baracca ◽  
Valentina Giorgio
Keyword(s):  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Mitochondrial Protein ◽  
High Energy ◽  
Neurocognitive Disorders ◽  
Human Diseases ◽  
Age Related ◽  
Muscle Tissues ◽  
Mitochondrial Atp Synthase ◽  
Genes Encoding

Human diseases range from gene-associated to gene-non-associated disorders, including age-related diseases, neurodegenerative, neuromuscular, cardiovascular, diabetic diseases, neurocognitive disorders and cancer. Mitochondria participate to the cascades of pathogenic events leading to the onset and progression of these diseases independently of their association to mutations of genes encoding mitochondrial protein. Under physiological conditions, the mitochondrial ATP synthase provides the most energy of the cell via the oxidative phosphorylation. Alterations of oxidative phosphorylation mainly affect the tissues characterized by a high-energy metabolism, such as nervous, cardiac and skeletal muscle tissues. In this review, we focus on human diseases caused by altered expressions of ATP synthase genes of both mitochondrial and nuclear origin. Moreover, we describe the contribution of ATP synthase to the pathophysiological mechanisms of other human diseases such as cardiovascular, neurodegenerative diseases or neurocognitive disorders.

P6277The impact of exercise training in combination with statin use on skeletal muscle mitochondrial oxidative phosphorylation and metabolomics in obese rats

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
I Urbaneck ◽  
F Lorenz ◽  
I Materzok ◽  
L Maletzki ◽  
M Pietzner ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cytochrome C ◽  
Exercise Training ◽  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Statin Treatment ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Complex Iv ◽  
Obese Rats ◽  
Statin Use

Abstract Background Exercise training (ET) and statin treatment both alter skeletal muscle function. Purpose We investigated the effects of a combined exercise and statin use on skeletal muscle mitochondrial oxidative phosphorylation (OxPhos) and metabolic alterations in obese rats. Methods Eight-week-old male Wistar rats were used. A total of 14 animals received standard chow, while 46 rats were fed a high-fat diet (HFD) for 20 weeks. After 8 weeks, the rats were randomized into 6 groups: sedentary (n=8), ET (n=6), sedentary with HFD (n=11), ET with HFD (n=11), statin with HFD (n=13) and ET with HFD and statins (n=11). Simvastatin (10mg/d/kg) was added to the drinking water. ET was performed for 12 weeks, 5 days/week for 1 h/day at 18 m/min in a motorized running wheel. OxPhos was assessed by complex-specific antibodies and targeted metabolomics using the Biocrates p180 kit. All experiments were done on frozen samples of the M. gastrocnemicus. An ANOVA with fixed effects for diet, exercise, statin treatment and statin-exercise interaction was used to identify significantly different metabolites. Results Statin use was associated with significantly lower cholesterol levels, but did not affect exercise duration and intensity compared to none-use. In sedentary animals, HFD increased OxPhos complex II (succinate dehydrogenase), complex IV (cytochrome-c-oxidase) and V (ATP synthase) while statin treatment diminished this increase in all complexes. HFD increased complex IV independent of statin treatment but had no effect on complex II and V in ET rats. Complex IV was increased due to ET only in HFD fed rats compared to rats on normal chow but decreased in contrast to sedentary animals on a HFD. With regards to metabolomics, we found 57 metabolites which were influenced by HFD while no metabolites were identified with a significant effect for ET. A significant statin-exercise interaction was found for three lysophosphatidylcholines (lysoPC a C26.0, lysoPC a C26.1, lysoPC a C24.0), one phosphatidylcholine (PC aa C42.6) and one sphingomyelin (SM C16.1). HFD decreased the concentration of all mentioned metabolites compared to standard chow fed animals. Likewise, ET increased the concentration of metabolites compared to sedentary animals on HFD. Statin treatment led to an increase, while statin in combination with ET did not rescue this effect. Conclusion HFD induced severely impaired skeletal muscle OxPhos independent of ET and statin treatment. Our findings suggest a limiting rate of NADH production in the tricarboxylic acid cycle as a potential mechanism. However, ET prevented the increase in cytochrome-c-oxidation while statins blocked the HFD induced increase in ATP synthase. Our metabolomics results imply that future research should consider the lipotoxic effects of a HFD when assessing skeletal muscle alterations due to ET or statins. Of particular interest could be the 5 metabolites that have been shown to be impacted by a statin-exercise interaction.

The fungal-specific subunit i/j of F1FO-ATP synthase stimulates the pathogenicity of Candida albicans independent of oxidative phosphorylation

2020 ◽  
Author(s):  
Yajing Zhao ◽  
Yan Lyu ◽  
Yanli Zhang ◽  
Shuixiu Li ◽  
Yishan Zhang ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Fungal Infections ◽  
Critical Role ◽  
Antifungal Drug ◽  
F1fo Atp Synthase

Abstract Invasive fungal infections are a major cause of human mortality due in part to a very limited antifungal drug arsenal. The identification of fungal-specific pathogenic mechanisms is considered a crucial step to current antifungal drug development and represents a significant goal to increase the efficacy and reduce host toxicity. Although the overall architecture of F1FO-ATP synthase is largely conserved in both fungi and mammals, the subunit i/j (Su i/j, Atp18) and subunit k (Su k, Atp19) are proteins not found in mammals and specific to fungi. Here, the role of Su i/j and Su k in Candida albicans was characterized by an in vivo assessment of the virulence and in vitro growth and mitochondrial function. Strikingly, the atp18Δ/Δ mutant showed significantly reduced pathogenicity in systemic murine model. However, this substantial defect in infectivity exists without associated defects in mitochondrial oxidative phosphorylation or proliferation in vitro. Analysis of virulence-related traits reveals normal in both mutants, but shows cell wall defects in composition and architecture in the case of atp18Δ/Δ. We also find that the atp18Δ/Δ mutant is more susceptible to attack by macrophages than wild type, which may correlate well with the abnormal cell wall function and increased sensitivity to oxidative stress. In contrast, no significant changes were observed in any of these studies for the atp19Δ/Δ. These results demonstrate that the fungal-specific Su i/j, but not Su k of F1FO-ATP synthase may play a critical role in C. albicans infectivity and represent another opportunity for new therapeutic target investigation. Lay Abstract This study aims to investigate biological functions of fungal-specific subunit i/j and subunit k of ATP synthase in C. albicans oxidative phosphorylation and virulence potential. Our results revealed that subunit i/j, and not subunit k, is critical for C. albicans pathogenicity.

scholarly journals Stepwise Assembly of Dimeric F1Fo-ATP Synthase in Mitochondria Involves the Small Fo-Subunits k and i

2010 ◽  
Vol 21 (9) ◽  
pp. 1494-1504 ◽  
Author(s):  
Karina Wagner ◽  
Inge Perschil ◽  
Christiane D. Fichter ◽  
Martin van der Laan
Keyword(s):  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Mitochondrial Membrane ◽  
Intermediate Form ◽  
Membrane Domains ◽  
Inner Mitochondrial Membrane ◽  
F1fo Atp Synthase ◽  
Key Enzyme ◽  
Stepwise Assembly ◽  
Oligomeric Forms

F1Fo-ATP synthase is a key enzyme of oxidative phosphorylation that is localized in the inner membrane of mitochondria. It uses the energy stored in the proton gradient across the inner mitochondrial membrane to catalyze the synthesis of ATP from ADP and phosphate. Dimeric and higher oligomeric forms of ATP synthase have been observed in mitochondria from various organisms. Oligomerization of ATP synthase is critical for the morphology of the inner mitochondrial membrane because it supports the generation of tubular cristae membrane domains. Association of individual F1Fo-ATP synthase complexes is mediated by the membrane-embedded Fo-part. Several subunits were mapped to monomer-monomer-interfaces of yeast ATP synthase complexes, but only Su e (Atp21) and Su g (Atp20) have so far been identified as crucial for the formation of stable dimers. We show that two other small Fo-components, Su k (Atp19) and Su i (Atp18) are involved in the stepwise assembly of F1Fo-ATP synthase dimers and oligomers. We have identified an intermediate form of the ATP synthase dimer, which accumulates in the absence of Su i. Moreover, our data indicate that Su i facilitates the incorporation of newly synthesized subunits into ATP synthase complexes.

scholarly journals Lichen fungi do not depend on the alga for ATP production

2021 ◽  
Author(s):  
Gulnara Tagirdzhanova ◽  
John McCutcheon ◽  
Toby Spribille
Keyword(s):  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Mitochondrial Genomes ◽  
Symbiotic Association ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Gene Encoding ◽  
Apparent Lack ◽  
Atp Production

Lichen fungi live in a symbiotic association with unicellular phototrophs and have no known aposymbiotic stage. A recent study postulated that some of them have lost mitochondrial oxidative phosphorylation and rely on their algal partners for ATP. This claim originated from an apparent lack of ATP9, a gene encoding one subunit of ATP synthase, from a few mitochondrial genomes. Here we show that while these fungi indeed have lost the mitochondrial ATP9, each retain a nuclear copy of this gene. Our analysis reaffirms that lichen fungi produce their own ATP.

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