Diverse functions of mitochondrial AAA+ proteins: protein activation, disaggregation, and degradationThis paper is one of a selection of papers published in this special issue entitled 8th International Conference on AAA Proteins and has undergone the Journal's usual peer review process.

Truscott, Kaye N.; Lowth, Bradley R.; Strack, Philip R.; Dougan, David A.

doi:10.1139/o09-167

Cited by 41 publications

(11 citation statements)

References 84 publications

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“…Chaperonin proteins, mHsp60 and mHsp10, are key players in the homeostasis of mitochondria since they mediate the folding of proteins in the matrix, an environment containing only a limited number of chaperones (in the human mitochondria there are only one Hsp60, one Hsp70 and no ClpB homologues) [56]. In addition to their chaperonin function, it is well documented that mHsp60 and mHsp10 affect processes that are not related directly to protein folding, such as apoptosis [16], [17] and inflammation [10]–[12].…”

Section: Discussionmentioning

confidence: 99%

Identification of Elements That Dictate the Specificity of Mitochondrial Hsp60 for Its Co-Chaperonin

et al. 2012

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Type I chaperonins (cpn60/Hsp60) are essential proteins that mediate the folding of proteins in bacteria, chloroplast and mitochondria. Despite the high sequence homology among chaperonins, the mitochondrial chaperonin system has developed unique properties that distinguish it from the widely-studied bacterial system (GroEL and GroES). The most relevant difference to this study is that mitochondrial chaperonins are able to refold denatured proteins only with the assistance of the mitochondrial co-chaperonin. This is in contrast to the bacterial chaperonin, which is able to function with the help of co-chaperonin from any source. The goal of our work was to determine structural elements that govern the specificity between chaperonin and co-chaperonin pairs using mitochondrial Hsp60 as model system. We used a mutagenesis approach to obtain human mitochondrial Hsp60 mutants that are able to function with the bacterial co-chaperonin, GroES. We isolated two mutants, a single mutant (E321K) and a double mutant (R264K/E358K) that, together with GroES, were able to rescue an E. coli strain, in which the endogenous chaperonin system was silenced. Although the mutations are located in the apical domain of the chaperonin, where the interaction with co-chaperonin takes place, none of the residues are located in positions that are directly responsible for co-chaperonin binding. Moreover, while both mutants were able to function with GroES, they showed distinct functional and structural properties. Our results indicate that the phenotype of the E321K mutant is caused mainly by a profound increase in the binding affinity to all co-chaperonins, while the phenotype of R264K/E358K is caused by a slight increase in affinity toward co-chaperonins that is accompanied by an alteration in the allosteric signal transmitted upon nucleotide binding. The latter changes lead to a great increase in affinity for GroES, with only a minor increase in affinity toward the mammalian mitochondrial co-chaperonin.

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Section: Discussionmentioning

confidence: 99%

Identification of Elements That Dictate the Specificity of Mitochondrial Hsp60 for Its Co-Chaperonin

et al. 2012

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“…Conversely, the C-terminal domain (amino acids 219–456) is highly homologous to the AAA+ (ATPases associated with various cellular activities) family, in which Bcs1-like proteins phylogenetically comprise their own AAA+ subfamily [112]. Mitochondria contain six AAA+ proteins of known function [113]: the m-AAA, i-AAA, and Lon proteases involved in mitochondrial protein quality control, Mcx1 and Hsp78, which are AAA+ proteins with classical chaperone-like functions in the mitochondrial matrix, and Bcs1. AAA+ ATPase family members bind ATP within a domain of 200–250 residues that contains conserved structural elements, including the Walker A, Walker B, and second region of homology (SRH) motifs.…”

Section: Eukaryotic Bc1 Complexesmentioning

confidence: 99%

Biogenesis of the cytochrome bc1 complex and role of assembly factors

Smith

Fox

Winge

2012

Biochimica et Biophysica Acta (BBA) - Bioenergetics

104

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The cytochrome bc1 complex is an essential component of the electron transport chain in most prokaryotes and in eukaryotic mitochondria. The catalytic subunits of the complex that are responsible for its redox functions are largely conserved across kingdoms. In eukarya, the bc1 complex contains supernumerary subunits in addition to the catalytic core, and the biogenesis of the functional bc1 complex occurs as a modular assembly pathway. Individual steps of this biogenesis have been recently investigated and are discussed in this review with an emphasis on the assembly of the bc1 complex in the model eukaryote Saccharomyces cerevisiae. Additionally, a number of assembly factors have been recently identified. Their roles in bc1 complex biogenesis are described, with special emphasis on the maturation and topogenesis of the yeast Rieske iron–sulfur protein and its role in completing the assembly of functional bc1 complex. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes.

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“…Mitochondria contain a number of AAA+ ATPases that can be traced to ancestral bacterial enzymes present during symbiogenesis (for review see Truscott et al, 2010). These proteins contain the family-specific sequence motifs responsible for ATP binding and hydrolysis, and presumably assemble into canonical ring-shaped oligomers (Hanson and Whiteheart, 2005).…”

Section: Introductionmentioning

confidence: 99%

Multifunctional Mitochondrial AAA Proteases

Glynn

2017

Front. Mol. Biosci.

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Mitochondria perform numerous functions necessary for the survival of eukaryotic cells. These activities are coordinated by a diverse complement of proteins encoded in both the nuclear and mitochondrial genomes that must be properly organized and maintained. Misregulation of mitochondrial proteostasis impairs organellar function and can result in the development of severe human diseases. ATP-driven AAA+ proteins play crucial roles in preserving mitochondrial activity by removing and remodeling protein molecules in accordance with the needs of the cell. Two mitochondrial AAA proteases, i-AAA and m-AAA, are anchored to either face of the mitochondrial inner membrane, where they engage and process an array of substrates to impact protein biogenesis, quality control, and the regulation of key metabolic pathways. The functionality of these proteases is extended through multiple substrate-dependent modes of action, including complete degradation, partial processing, or dislocation from the membrane without proteolysis. This review discusses recent advances made toward elucidating the mechanisms of substrate recognition, handling, and degradation that allow these versatile proteases to control diverse activities in this multifunctional organelle.

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Diverse functions of mitochondrial AAA+ proteins: protein activation, disaggregation, and degradationThis paper is one of a selection of papers published in this special issue entitled 8th International Conference on AAA Proteins and has undergone the Journal's usual peer review process.

Cited by 41 publications

References 84 publications

Identification of Elements That Dictate the Specificity of Mitochondrial Hsp60 for Its Co-Chaperonin

Identification of Elements That Dictate the Specificity of Mitochondrial Hsp60 for Its Co-Chaperonin

Biogenesis of the cytochrome bc1 complex and role of assembly factors

Multifunctional Mitochondrial AAA Proteases

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