Structure–function relationships in mitochondrial complex I of the strictly aerobic yeast <i>Yarrowia lipolytica</i>

Brandt, Ulrich; Abdrakhmanova, Albina; Zickermann, Volker; Galkin, Alexander; Dröse, Stefan; Zwicker, Klaus; Kerscher, Stefan

doi:10.1042/bst0330840

Cited by 18 publications

(14 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Eukaryotic enzymes contain more subunits, e.g. 32 in Neurospora crassa (Tuschen et al 1990;Nehls et al 1992), 40 in the yeast Yarrowia lipolytica (Abdrakhmanova et al 2004;Brandt et al 2005;Morgner et al 2008), and at least 45 in the bovine enzyme (Hirst et al 2003;. The number of Fe-S clusters also differs.…”

Section: Differences Between Nadh:ubiquinone Oxidoreductases From Difmentioning

confidence: 94%

The reaction of NADPH with bovine mitochondrial NADH:ubiquinone oxidoreductase revisited

Albracht

2010

J Bioenerg Biomembr

View full text Add to dashboard Cite

The first purification of bovine NADH:ubiquinone oxidoreductase (Complex I) was reported nearly half a century ago (Hatefi et al. J Biol Chem 237:1676-1680, 1962. The pathway of electron-transfer through the enzyme is still under debate. A major obstacle is the assignment of EPR signals to the individual iron-sulfur clusters in the subunits. The preceding paper described a working model based on the kinetics with NADPH. This model is at variance with current views in the field. The present paper provides a critical overview on the possible causes for the discrepancies. It is concluded that the stability of all purified preparations described thus far, including Hatefi's Complex I, is compromised due to removal of the enzyme from the protective membrane environment. In addition, most preparations described during the last two decades are purified by methods involving synthetic detergents and column chromatography. This results in delipidation, loss of endogenous quinones and loss of reactions with (artificial) quinones in a rotenone-sensitive way. The Fe:FMN ratio's indicate that FMN-a is absent, but that all Fe-S clusters may be present. In contrast to the situation in bovine SMP and Hatefi's Complex I, three of the six expected [4Fe-4S] clusters are not detected in EPR spectra. Qualitatively, the overall EPR lineshape of the remaining three cubane signals may seem similar to that of Hatefi's Complex I, but quantitatively it is not. It is further proposed that point mutations in any of the TYKY, PSST, 49-kDa or 30-kDa subunits, considered to make up the delicate structural heart of Complex I, may have unpredictable effects on any of the other subunits of this quartet. The fact that most point mutations led to inactive enzymes makes a correct interpretation of such mutations even more ambiguous. In none of the Complex-Icontaining membrane preparations from non-bovine origin, the pH dependencies of the NAD(P)H→O 2 reactions and the pH-dependent reduction kinetics of the Fe-S clusters with NADPH have been determined. This excludes a proper discussion on the absence or presence of FMN-a in native Complex I from other organisms.

show abstract

Section: Differences Between Nadh:ubiquinone Oxidoreductases From Difmentioning

confidence: 94%

The reaction of NADPH with bovine mitochondrial NADH:ubiquinone oxidoreductase revisited

Albracht

2010

J Bioenerg Biomembr

View full text Add to dashboard Cite

show abstract

“…Eight predicted STMD subunits were found in Y. lipolytica complex I [7] and as much as 14 in the bovine enzyme [17]. The function of STMD subunits is not clear but it has been proposed that they may assist assembly and are important for maintaining structural integrity [68]. In addition, accessory subunit B14.7 (from bovine heart, corresponding to NUJM of Y. lipolytica ) and the fungi-specific NUXM protein have three and two predicted transmembrane helices, respectively.…”

Section: The Membrane Armmentioning

confidence: 99%

Architecture of complex I and its implications for electron transfer and proton pumping

Zickermann

Kerscher

Zwicker

et al. 2009

Biochimica et Biophysica Acta (BBA) - Bioenergetics

View full text Add to dashboard Cite

Proton pumping NADH:ubiquinone oxidoreductase (complex I) is the largest and remains by far the least understood enzyme complex of the respiratory chain. It consists of a peripheral arm harbouring all known redox active prosthetic groups and a membrane arm with a yet unknown number of proton translocation sites. The ubiquinone reduction site close to iron-sulfur cluster N2 at the interface of the 49-kDa and PSST subunits has been mapped by extensive site directed mutagenesis. Independent lines of evidence identified electron transfer events during reduction of ubiquinone to be associated with the potential drop that generates the full driving force for proton translocation with a 4 H+/2e− stoichiometry. Electron microscopic analysis of immuno-labelled native enzyme and of a subcomplex lacking the electron input module indicated a distance of 35–60 Å of cluster N2 to the membrane surface. Resolution of the membrane arm into subcomplexes showed that even the distal part harbours subunits that are prime candidates to participate in proton translocation because they are homologous to sodium/proton antiporters and contain conserved charged residues in predicted transmembrane helices. The mechanism of redox linked proton translocation by complex I is largely unknown but has to include steps where energy is transmitted over extremely long distances. In this review we compile the available structural information on complex I and discuss implications for complex I function.

show abstract

“…Yarrowia lipolytica is a dimorphic fungus that has become a well‐established yeast model for studies of protein secretion (Le Dall et al ., ; Pertuiset et al ., ; Dominguez et al ., ; Ruiz‐Pavon & Dominguez, ; Ogrydziak & Nicaud, ), mitochondrial bioenergetics (Brandt et al ., ) and cell morphogenesis and differentiation (Barth & Gaillardin, ; Torres‐Guzman & Dominguez, ; Szabo, , Cervantes‐Chavez & Ruiz‐Herrera, ; Cervantes‐Chavez et al ., ; Gonzalez‐Lopez et al ., ). Recently, Y. lipolytica has been also introduced as a model for telomere research because the organism lacks a number of telomere proteins that are present in other yeast (Kinsky et al ., ).…”

Section: Introductionmentioning

confidence: 99%

TheRAD52ortholog ofYarrowia lipolyticais essential for nuclear integrity and DNA repair

et al. 2013

View full text Add to dashboard Cite

Yarrowia lipolytica (Yl) is a dimorphic fungus that has become a well-established model for a number of biological processes, including secretion of heterologous and chimerical proteins. However, little is known on the recombination machinery responsible for the integration in the genome of the exogenous DNA encoding for those proteins. We have carried out a phenotypic analysis of rad52 deletants of Y. lipolytica. YlRad52 exhibited 20-30% identity with Rad52 homologues of other eukaryotes, including Saccharomyces cerevisiae and Candida albicans. Ylrad52-Δ strains formed colonies on YPD-agar plates which were spinier and smaller than those from wild type, whereas in YPD liquid cultures they exhibited a decreased grow rate and contained cells with aberrant morphology and fragmented chromatin, supporting a role for homologous recombination (HR) in genome stability under nondamaging conditions. In addition, Ylrad52 mutants showed moderate to high sensitivity to UV light, oxidizing agents and compounds that cause single- (SSB) and double-strand breaks (DSB), indicating an important role for Rad52 in DNA repair. These findings extend to Yl previous observations indicating that RAD52 is a crucial gene for DNA repair in other fungi, including S. cerevisiae, C. albicans and Schizosaccharomyces pombe.

show abstract

Structure–function relationships in mitochondrial complex I of the strictly aerobic yeast Yarrowia lipolytica

Cited by 18 publications

References 39 publications

The reaction of NADPH with bovine mitochondrial NADH:ubiquinone oxidoreductase revisited

The reaction of NADPH with bovine mitochondrial NADH:ubiquinone oxidoreductase revisited

Architecture of complex I and its implications for electron transfer and proton pumping

TheRAD52ortholog ofYarrowia lipolyticais essential for nuclear integrity and DNA repair

Contact Info

Product

Resources

About