Introduction of the Chloroplast Redox Regulatory Region in the Yeast ATP Synthase Impairs Cytochrome c Oxidase

Shen, Hong; Walters, D. Eric; Mueller, David M.

doi:10.1074/jbc.m805310200

Cited by 9 publications

(6 citation statements)

References 42 publications

(26 reference statements)

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“…While it is not uncommon for mutations in genes encoding mitochondrial proteins to exhibit pleiotropic effects, this effect was unusual in that the levels of cytochromes a + a 3 , c + c 1 , and b were unaltered suggesting that activity could be altered without altering synthesis or stability of the cytochromes. This and an unrelated study 78 suggest a link, which will be discussed later, between the ATP synthase and the respiratory chain.…”

Section: Structure and Organization Of The F 1 F mentioning

confidence: 71%

Understanding structure, function, and mutations in the mitochondrial ATP synthase

Pagadala

Mueller

2015

MIC

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The mitochondrial ATP synthase is a multimeric enzyme complex with an overall molecular weight of about 600,000 Da. The ATP synthase is a molecular motor composed of two separable parts: F1 and Fo. The F1 portion contains the catalytic sites for ATP synthesis and protrudes into the mitochondrial matrix. Fo forms a proton turbine that is embedded in the inner membrane and connected to the rotor of F1. The flux of protons flowing down a potential gradient powers the rotation of the rotor driving the synthesis of ATP. Thus, the flow of protons though Fo is coupled to the synthesis of ATP. This review will discuss the structure/function relationship in the ATP synthase as determined by biochemical, crystallographic, and genetic studies. An emphasis will be placed on linking the structure/function relationship with understanding how disease causing mutations or putative single nucleotide polymorphisms (SNPs) in genes encoding the subunits of the ATP synthase, will affect the function of the enzyme and the health of the individual. The review will start by summarizing the current understanding of the subunit composition of the enzyme and the role of the subunits followed by a discussion on known mutations and their effect on the activity of the ATP synthase. The review will conclude with a summary of mutations in genes encoding subunits of the ATP synthase that are known to be responsible for human disease, and a brief discussion on SNPs.

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Section: Structure and Organization Of The F 1 F mentioning

confidence: 71%

Understanding structure, function, and mutations in the mitochondrial ATP synthase

Pagadala

Mueller

2015

MIC

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“…This change in redox-state does not affect ATP binding rates to the catalytic site(s) or torque for rotation, but instead causes a long pause in the catalytic process due to ADP inhibition (Kim et al 2011). Introducing this redox-sensitive amino acid sequence from the plant into the yeast γ-subunit has been found to cause a defect in oxidative phosphorylation (Shen et al 2008). …”

Section: Introductionmentioning

confidence: 99%

Redox Regulation of Mitochondrial ATP Synthase

Wang

Murray

Chung

et al. 2013

Trends in Cardiovascular Medicine

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Reversible cysteine oxidative post-translational modifications (Ox-PTMs) represent an important mechanism to regulate protein structure and function. In mitochondria, redox-reactions can modulate components of the electron transport chain (ETC), the F1FO-ATP synthase complex and other matrix proteins/enzymes. Emerging evidence has linked Ox-PTMs to mitochondrial dysfunction and heart failure, highlighting some potential therapeutic avenues. Ox-PTMs can modify a variety of amino acid residues, including cysteine, and have the potential to modulate the function of a large number of proteins. Among this group, there is a selected subset of amino acid residues that can function as redox-switches. These unique sites are proposed to monitor the cell's oxidative balance through their response to the various Ox-PTMs. In this review, the role of Ox-PTMs in the regulation of the F1FO-ATP synthase complex is discussed in the context of heart failure and its possible clinical treatment.

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“…12 As well, introducing the redox modulated region of the plant ATPase into the yeast gamma-subunit causes a defect in oxidative phosphorylation. 13 …”

Section: Introductionmentioning

confidence: 99%

Redox Regulation of Mitochondrial ATP Synthase

Wang

Foster

Rucker

et al. 2011

Circulation Research

141

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Rationale Cardiac resynchronization therapy (CRT) is an effective clinical treatment for heart failure patients with conduction delay, impaired contraction and energetics. Our recent studies have revealed that mitochondrial post-translational modifications (PTM) may contribute to its benefits, motivating the present study of the oxidative regulation of mitochondrial ATP synthase. Objectives Here, we tested whether CRT alteration of ATP synthase function is linked to cysteine (Cys) oxidative PTM (Ox-PTM) of specific ATP synthase subunits. Methods and Results Canine left ventricular myocardium was collected under conditions to preserve Ox-PTM from control, dyssynchronous heart failure (DHF) or hearts that have undergone CRT. In-gel ATPase activity showed that CRT increased ATPase activity by ~2 fold (p<0.05) over DHF, approaching control levels and this effect was recapitulated with a reducing agent. ATP synthase function and three Ox-PTM: disulfide bond, S-glutathionylation and S-nitrosation were assessed. ATP synthase from DHF hearts contained two novel disulfide bonds, between ATP synthase alpha subunits themselves and between alpha and gamma subunits, both of which were decreased in CRT hearts (4.38±0.13 and 4.23±0.36-fold, respectively, p<0.01). S-glutathionylation of ATP synthase alpha subunit occurred in DHF hearts and was reversed by CRT (1.56±0.16-fold, p<0.04). In contrast, S-nitrosation of ATP synthase alpha subunit in DHF hearts was lower than in CRT hearts (1.53±0.19-fold, p<0.05). All modifications occurred at ATP synthase alpha subunit Cys294 and Cys to Ser mutation indicated that this residue is critical for ATP synthase function. Conclusions A selective Cys in ATP synthase alpha subunit is targeted by multiple Ox-PTM suggesting that this Cys residue may act as a redox sensor modulating ATP synthase function.

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Introduction of the Chloroplast Redox Regulatory Region in the Yeast ATP Synthase Impairs Cytochrome c Oxidase

Cited by 9 publications

References 42 publications

Understanding structure, function, and mutations in the mitochondrial ATP synthase

Understanding structure, function, and mutations in the mitochondrial ATP synthase

Redox Regulation of Mitochondrial ATP Synthase

Redox Regulation of Mitochondrial ATP Synthase

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