The Gating and Coupling Function of Mitochondrial, H+ ATP Synthase. Role of Fo and F1 Subunits

1994 ◽  
pp. 19-39
Author(s):  
S. Papa
Keyword(s):  
Atp Synthase ◽  
Coupling Function

scholarly journals Role of F0 and F1 subunits in the gating and coupling function of mitochondrial H+-ATP synthase. The effect of dithiol reagents

1992 ◽  
Vol 208 (1) ◽  
pp. 9-16 ◽  
Author(s):  
Franco ZANOTTI ◽  
Ferruccio GUERRIERI ◽  
Giuseppe CAPOZZA ◽  
Maria FIERMONTE ◽  
Jan BERDEN ◽  
...  
Keyword(s):  
Atp Synthase ◽  
Coupling Function

The F1Fo-ATPase inhibitor, IF1, is a critical regulator of energy metabolism in cancer cells

2021 ◽  
Vol 49 (2) ◽  
pp. 815-827
Author(s):  
Giancarlo Solaini ◽  
Gianluca Sgarbi ◽  
Alessandra Baracca
Keyword(s):  
Cancer Cells ◽  
Atp Synthase ◽  
Aerobic Glycolysis ◽  
Cell Metabolism ◽  
Metabolic Reprogramming ◽  
Endogenous Inhibitor ◽  
Atpase Inhibitor ◽  
Molecular Action ◽  
F1fo Atpase

In the last two decades, IF1, the endogenous inhibitor of the mitochondrial F1Fo-ATPase (ATP synthase) has assumed greater and ever greater interest since it has been found to be overexpressed in many cancers. At present, several findings indicate that IF1 is capable of playing a central role in cancer cells by promoting metabolic reprogramming, proliferation and resistance to cell death. However, the mechanism(s) at the basis of this pro-oncogenic action of IF1 remains elusive. Here, we recall the main features of the mechanism of the action of IF1 when the ATP synthase works in reverse, and discuss the experimental evidence that support its relevance in cancer cells. In particular, a clear pro-oncogenic action of IF1 is to avoid wasting of ATP when cancer cells are exposed to anoxia or near anoxia conditions, therefore favoring cell survival and tumor growth. However, more recently, various papers have described IF1 as an inhibitor of the ATP synthase when it is working physiologically (i.e. synthethizing ATP), and therefore reprogramming cell metabolism to aerobic glycolysis. In contrast, other studies excluded IF1 as an inhibitor of ATP synthase under normoxia, providing the basis for a hot debate. This review focuses on the role of IF1 as a modulator of the ATP synthase in normoxic cancer cells with the awareness that the knowledge of the molecular action of IF1 on the ATP synthase is crucial in unravelling the molecular mechanism(s) responsible for the pro-oncogenic role of IF1 in cancer and in developing related anticancer strategies.

Role of γ-Subunit N- and C-Termini in Assembly of the Mitochondrial ATP Synthase in Yeast

2008 ◽  
Vol 377 (5) ◽  
pp. 1314-1323 ◽  
Author(s):  
Elke A. Dian ◽  
Panagiotis Papatheodorou ◽  
Kerstin Emmrich ◽  
Olga Randel ◽  
Andreas Geissler ◽  
...  
Keyword(s):  
Atp Synthase ◽  
Γ Subunit ◽  
Mitochondrial Atp Synthase

scholarly journals On the Role of Arg-210 and Glu-219 of Subunitain Proton Translocation by theEscherichia coliF0F1-ATP Synthase

1997 ◽  
Vol 272 (51) ◽  
pp. 32635-32641 ◽  
Author(s):  
Francis I. Valiyaveetil ◽  
Robert H. Fillingame
Keyword(s):  
Atp Synthase ◽  
Proton Translocation

The role of formation of pyrrole–ATP synthase subunit beta adduct in pyrrolizidine alkaloid-induced hepatotoxicity

2018 ◽  
Vol 92 (11) ◽  
pp. 3403-3414 ◽  
Author(s):  
Yao Lu ◽  
Jiang Ma ◽  
Zijing Song ◽  
Yang Ye ◽  
Peter P. Fu ◽  
...  
Keyword(s):  
Atp Synthase ◽  
Pyrrolizidine Alkaloid

Abstract MP247: Mitochondrial Complex V Is Regulated By GRK2 In The Heart

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Kimberly Ferrero ◽  
Jessica M Pfleger ◽  
Kurt Chuprun ◽  
Eric Barr ◽  
Erhe Gao ◽  
...  
Keyword(s):  
Atp Synthase ◽  
Cardiac Injury ◽  
Atp Synthesis ◽  
Cardiac Metabolism ◽  
Neonatal Rat ◽  
Interacting Proteins ◽  
Atp Production

The GPCR kinase GRK2 is highly expressed the heart; importantly, during cardiac injury or heart failure (HF) both levels and activity of GRK2 increase. The role of GRK2 during HF is canonically studied upstream of β-adrenergic desensitization. However, GRK2 has a large interactome and noncanonical functions for this kinase are being uncovered. We have discovered that in the heart, GRK2 translocates to mitochondria ( mtGRK2 ) following injury and is associated with negative effects on cardiac metabolism. Thus, we have sought to identify the mechanism(s) by which GRK2 can regulate mitochondrial function. We hypothesize that mtGRK2 interacts with proteins which regulate bioenergetics and substrate utilization, and this never-before-described role may partially explain the altered mitochondrial phenotype seen following cardiac injury or HF. Stress-induced mitochondrial translocation of GRK2 was validated in neonatal rat ventricular myocytes, murine heart tissue and a cardiac-derived cell line. Consequently, the GRK2 interactome was mapped basally and under stress conditions in vitro, in vivo , and with tagged recombinant peptides. GRK2-interacting proteins were isolated via immunoprecipitation and analyzed via liquid chromatography-mass spectroscopy (LCMS). Proteomics analysis (IPA; Qiagen) identified mtGRK2 interacting proteins which were also involved in mitochondrial dysfunction. Excitingly, Complexes I, II, IV and V (ATP synthase) of the electron transport chain (ETC) were identified in the subset of mtGRK2-dysfunction partners. Several mtGRK2-ETC interactions were increased following stress, particularly those in Complex V. We further established that mtGRK2 phosphorylates some of the subunits of Complex V, particularly the ATP synthase barrel which is critical for ATP production in the heart. Specific amino acid residues on these subunits have been identified using PTM-LCMS and are currently being validated in a murine model of myocardial infarction. To support these data, we have also determined that alterations in either the levels or kinase activity of GRK2 appear to alter the enzymatic activity of Complex V in vitro , thus altering ATP production. In summary, the phosphorylation of the ATP synthesis machinery by mtGRK2 may be regulating some of the phenotypic effects of injured or failing hearts such as increased ROS production and reduced fatty acid metabolism. Research is ongoing in our lab to elucidate the novel role of GRK2 in regulating mitochondrial bioenergetics and cell death, thus uncovering an exciting, druggable novel target for rescuing cardiac function in patients with injured and/or failing hearts.

The Perennial Riddle of Life’s Origin

2021 ◽  
pp. 82-96
Author(s):  
Franklin M. Harold
Keyword(s):  
Natural Selection ◽  
Electron Transport ◽  
Atp Synthase ◽  
Hydrothermal Vents ◽  
Rna World ◽  
Good Reason ◽  
Dynamic Network ◽  
Electron Transport Chains ◽  
The Origin Of Life

The origin of life is the most consequential problem in biology, possibly in all of science, and it remains unsolved. This chapter summarizes what has been learned and highlights questions that remain open, including How, Where, When, and especially Why. LUCA, some four billion years ago, already featured the basic capacities of contemporary cells. These must have evolved still earlier, at a nebulous proto-cellular stage. There is good reason to believe that enzymes, DNA, ribosomes, electron-transport chains, and the rotary ATP synthase all predate LUCA and were shaped by the standard process of variation and natural selection, but we know next to nothing about how cells ever got started. I favor the proposal that it began with a purely chemical dynamic network capable of reproducing itself, that may have originated by chance. Natural selection would have favored the incorporation of any ancillary factors that promoted its kinetic stability, especially ones that improved reproduction or gave access to energy. All the specifics are in dispute, including the role of a prebiotic broth of organic chemicals, the nature and origin of enclosure, the RNA world, and a venue in submarine hydrothermal vents. My sense is that critical pieces of the puzzle remain to be discovered.

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