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Smeitink, Jan A.M.; Sengers, R. C. A.; Trijbels, Frans J.M.; Heuvel, Lambert van den

doi:10.1023/a:1010743321800

Cited by 111 publications

(21 citation statements)

References 40 publications

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“…Therefore, we looked at submitochondrial localization of these proteins. Respiratory complex I contains at least 44 different proteins residing in either the matrix arm or hydrophobic intermembrane region of the holocomplex (Smeitink et al ., 2001; Janssen et al ., 2006). Thirty‐eight of the 44 complex I proteins were detected in our proteomic analyses.…”

Section: Resultsmentioning

confidence: 99%

“…Complex I is the largest and most intricate respiratory enzyme, the primary entry site of electrons into the respiratory chain, implicated in many disease states, including Leigh syndrome, and the enzyme most often affected in respiratory disorders (Kirby et al ., 1999; Loeffen et al ., 2000; Smeitink et al ., 2001; Kruse et al ., 2008). Abundance of every complex I subunit in the EDL was increased among those that showed any change in abundance with age.…”

Section: Discussionmentioning

confidence: 99%

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Age modifies respiratory complex I and protein homeostasis in a muscle type‐specific manner

et al. 2015

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SummaryChanges in mitochondrial function with age vary between different muscle types, and mechanisms underlying this variation remain poorly defined. We examined whether the rate of mitochondrial protein turnover contributes to this variation. Using heavy label proteomics, we measured mitochondrial protein turnover and abundance in slow‐twitch soleus (SOL) and fast‐twitch extensor digitorum longus (EDL) from young and aged mice. We found that mitochondrial proteins were longer lived in EDL than SOL at both ages. Proteomic analyses revealed that age‐induced changes in protein abundance differed between EDL and SOL with the largest change being increased mitochondrial respiratory protein content in EDL. To determine how altered mitochondrial proteomics affect function, we measured respiratory capacity in permeabilized SOL and EDL. The increased mitochondrial protein content in aged EDL resulted in reduced complex I respiratory efficiency in addition to increased complex I‐derived H2O2 production. In contrast, SOL maintained mitochondrial quality, but demonstrated reduced respiratory capacity with age. Thus, the decline in mitochondrial quality with age in EDL was associated with slower protein turnover throughout life that may contribute to the greater decline in mitochondrial dysfunction in this muscle. Furthermore, mitochondrial‐targeted catalase protected respiratory function with age suggesting a causal role of oxidative stress. Our data clearly indicate divergent effects of age between different skeletal muscles on mitochondrial protein homeostasis and function with the greatest differences related to complex I. These results show the importance of tissue‐specific changes in the interaction between dysregulation of respiratory protein expression, oxidative stress, and mitochondrial function with age.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Age modifies respiratory complex I and protein homeostasis in a muscle type‐specific manner

et al. 2015

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“…The bovine enzyme has also provided a model for characterizing the much less readily available human enzyme (20). Mutations in subunits of human complex I have been associated with neurological and neuromuscular diseases (21).…”

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confidence: 99%

Bovine Complex I Is a Complex of 45 Different Subunits

Carroll

Fearnley

Skehel³

et al. 2006

Journal of Biological Chemistry

427

309

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Mammalian mitochondrial complex I is a multisubunit membrane-bound assembly with a molecular mass approaching 1 MDa. By comprehensive analyses of the bovine complex and its constituent subcomplexes, 45 different subunits have been characterized previously. The presence of a 46th subunit was suspected from the consistent detection of a molecular mass of 10,566 by electrospray ionization mass spectrometry of subunits fractionated by reverse-phase high pressure liquid chromatography. The component was found associated with both the intact complex and subcomplex I␤, which represents most of the membrane arm of the complex, and it could not be resolved chromatographically from subunit SGDH (the subunit of bovine complex I with the N-terminal sequence Ser-Gly-Asp-His). It has now been characterized by tandem mass spectrometry of intact protein ions and shown to be a C-terminal fragment of subunit SGDH arising from a specific peptide bond cleavage between Ile-55 and Pro-56 during the electrospray ionization process. Thus, the subunit composition of bovine complex I has been established. It is a complex of 45 different proteins plus non-covalently bound FMN and eight iron-sulfur clusters.

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“…1). Diminished complex I activity is associated with Parkinson's disease (3) and aging (4) and represents the most frequently encountered inherited defect of the oxidative phosphorylation (OXPHOS) system (5). Despite considerable knowledge of primary sequences (6), cofactors (7), and assembly (8), the mechanism of redox-driven proton transport by complex I and the subunit(s) that guide the proton through its membranous part is unknown.…”

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confidence: 99%

Sodium ion cycling mediates energy coupling between complex I and ATP synthase

Gemperli

Dimroth²,

Steuber³

2003

Proc. Natl. Acad. Sci. U.S.A.

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We show here sodium ion cycling between complex I from Klebsiella pneumoniae and the F 1F0 ATP synthase from Ilyobacter tartaricus in a reconstituted proteoliposome system. In the course of NADH oxidation by complex I, an electrochemical sodium ion gradient was established and served as a driving force for the synthesis of ATP from ADP and phosphate. In the opposite direction, the ⌬˜N a ؉ generated by ATP hydrolysis could be coupled to NADH formation by reversed electron transfer from ubiquinol to NAD. For reverse electron transfer, a transmembrane voltage larger than 30 mV was obligatory. No NADH-driven proton transport into the lumen of proteoliposomes was detected. We conclude that Na ؉ is used as the exclusive coupling ion by the enterobacterial complex I. E very living cell establishes transmembrane electrochemical gradients with the help of primary ion pumps. These power plants of the cell provide or use energy-rich metabolites like ATP or NADH. The chemiosmotic theory (1) describes how the exergonic oxidation of NADH by the NADH:quinone oxidoreductase (complex I) generates an electrochemical potential that drives the endergonic synthesis of ATP by ATP synthase. Homologues of these two enzyme complexes are found in the inner membrane of mitochondria, in the thylakoid membrane of chloroplasts, and in the cytoplasmic membrane of bacteria. Complex I is a large lipoprotein complex (500 or 1,000 kDa in bacteria or eukaryotes) that couples the oxidation of NADH with quinones to the transport of protons (2) across the membrane. The redox cofactors of complex I (one FMN and up to nine Fe͞S clusters) are located in the promontory arm of the L-shaped complex extending into the cytoplasm, whereas the coupling cations (H ϩ or Na ϩ ) must pass through the membranous part of the complex (Fig. 1). Diminished complex I activity is associated with Parkinson's disease (3) and aging (4) and represents the most frequently encountered inherited defect of the oxidative phosphorylation (OXPHOS) system (5). Despite considerable knowledge of primary sequences (6), cofactors (7), and assembly (8), the mechanism of redox-driven proton transport by complex I and the subunit(s) that guide the proton through its membranous part is unknown. A promising approach is to study bacterial counterparts of complex I that are smaller but possess all central subunits required for redox-driven H ϩ (or Na ϩ ) transport (9). In particular, an Na ϩ -translocating complex I found in enterobacteria like Escherichia coli (10) or Klebsiella pneumoniae (11) is a useful model to trace the pathway of the coupling cation, as exemplified by the Na ϩ -translocating F 1 F 0 ATP synthase (12). The analysis of the cation-translocating step is facilitated by selectively removing or adding Na ϩ , which does not affect the stability of the protein. Variation of the proton concentration is far more restricted, however, because the physiologically active proteins usually tolerate proton concentrations of 10 Ϫ8 to 10 Ϫ6 M. By using Na ϩ -rather than H ϩ -translocating ...

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Untitled

Cited by 111 publications

References 40 publications

Age modifies respiratory complex I and protein homeostasis in a muscle type‐specific manner

Age modifies respiratory complex I and protein homeostasis in a muscle type‐specific manner

Bovine Complex I Is a Complex of 45 Different Subunits

Sodium ion cycling mediates energy coupling between complex I and ATP synthase

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