The oligomycin sensitivity conferring protein (OSCP) of beef heart mitochondria: Studies of its binding to F1 and its function

Hundal, Torill; Norling, Birgitta; Ernster, Lars

doi:10.1007/bf00743244

Cited by 18 publications

(4 citation statements)

References 35 publications

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“…It was, however, not efficiently associated with the subunits constituting the stalk linking F1 to F0 since the ATPase activity was cold-labile. Indeed, it has been shown in beef heart F1 that the binding of isolated F1 to OSCP (30,12) or to other subunits constituting the stalk such as subunits b, F6, and d (12) decreases F1 sensitivity to cold exposure. Therefore, the cold-sensitivity of the F1-ATPase in human °cells indicates that at least some of the stalk subunits are deficient.…”

Section: Discussionmentioning

confidence: 99%

Functional F1-ATPase Essential in Maintaining Growth and Membrane Potential of Human Mitochondrial DNA-depleted ρ° Cells

Buchet

Godinot

1998

Journal of Biological Chemistry

219

175

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F1-ATPase assembly has been studied in human °c ells devoid of mitochondrial DNA (mtDNA). Since, in these cells, oxidative phosphorylation cannot provide ATP, their growth relies on glycolysis. Despite the absence of the mtDNA-coded F0 subunits 6 and 8, °cells possessed normal levels of F1-ATPase ␣ and ␤ subunits. This F1-ATPase was functional and azide-or aurovertinsensitive but oligomycin-insensitive. In addition, aurovertin decreased cell growth in °cells and also reduced their mitochondrial membrane potential, as measured by rhodamine 123 fluorescence. Therefore, a functional F1-ATPase was important to maintain the mitochondrial membrane potential and the growth of these °c ells. Bongkrekic acid, a specific adenine nucleotide translocator (ANT) inhibitor, also reduced °cell growth and mitochondrial membrane potential. In conclusion, °cells need both a functional F1-ATPase and a functional ANT to maintain their mitochondrial membrane potential, which is necessary for their growth. ATP hydrolysis catalyzed by F1 must provide ADP 3؊ at a sufficient rate to maintain a rapid exchange with the glycolytic ATP 4؊ by ANT, this electrogenic exchange inducing a mitochondrial membrane potential efficient enough to sustain cell growth. However, since the effects of bongkrekic acid and of aurovertin were additive, other electrogenic pumps should cooperate with this pathway.The biogenesis of mitochondrial proteins is controlled by both nuclear and mitochondrial genomes. The proteins coded by the mtDNA are subunits of enzyme complexes involved in oxidative phosphorylation. Since all these complexes also contain proteins coded by the nuclear genome, mechanisms regulating the coordinated expression and assembly of the subunits of nuclear and mitochondrial origin must exist. In yeast cells, nuclear DNA-coded components continue to be synthesized and imported into mitochondria, even when the synthesis of mtDNA-coded subunits is blocked (cf. for review, Refs. 1 and 2). The groups of Schatz and co-workers (3) and Neupert (4) have shown that a mitochondrial membrane potential is a key requirement for protein import into mitochondria (5). In normal cells, the mitochondrial membrane potential is mainly maintained by transmembrane proton pumping occurring during electron transfer or during ATP hydrolysis catalyzed by the ATPase-ATP synthase. In °cells depleted of mtDNA, these complexes cannot be functional since all complexes involved in proton pumping contain mtDNA-coded subunits (6). However, proteins of nuclear origin are imported into the °cell mitochondria (7). Therefore, the mitochondrial membrane potential must be maintained by other electrogenic pumps. In yeast, it has been suggested that the adenine nucleotide translocator (ANT) 1 mediates an exchange of ATP 4Ϫ synthesized in the cytosol during glycolysis for ADP 3Ϫ to maintain this mitochondrial membrane potential (8). However, the exact mechanism that maintains this potential has not been thoroughly investigated. Since the mtDNA-coded subunits are essential components for ...

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Section: Discussionmentioning

confidence: 99%

Functional F1-ATPase Essential in Maintaining Growth and Membrane Potential of Human Mitochondrial DNA-depleted ρ° Cells

Buchet

Godinot

1998

Journal of Biological Chemistry

219

175

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“…FI affords some protection against trypsin proteolysis of either the b-subunit of E. coli (Hermolin et al, 1983;Perlin et al, 1983;Hoppe et al, 1983) or OSCP (Hundal et al, 1984). The trypsin cleavable segment of the b-subunit is not required for proton translocation through F0 (Hermolin et al, 1983;Perlin et al, 1983;Hoppe et al, 1983) although the b-subunit is compulsory for the reconstitution of proton translocation (Schneider & Altendorf, 1984).…”

Section: Discussionmentioning

confidence: 99%

Topography of oligomycin sensitivity conferring protein in the mitochondrial adenosine triphosphatase-ATP synthase

Archinard¹,

Godinot²,

Comte³

et al. 1986

Biochemistry

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The topographical organization of oligomycin sensitivity conferring protein (OSCP) in the mitochondrial adenosinetriphosphatase (ATPase)-ATP synthase complex has been studied. The accessibility of OSCP to monoclonal antibodies has been qualitatively visualized by using the protein A-gold electron microscopy immunocytochemistry or quantitatively estimated by immunotitration of OSCP in depolymerized or intact membranes. Besides, OSCP cannot be labeled by 3-(trifluoromethyl)-3-(m-[125I]iodophenyl)diazirine ([125I]TID) which selectively labels the hydrophobic core of membrane proteins. These observations demonstrate an external location of OSCP on the inner face of the inner mitochondrial membrane. The position of OSCP relative to other peptides of the complex has been analyzed by cross-linking experiments using either zero length N-(ethoxycarbonyl)-2-ethoxydihydroquinoline or 11-A span dimethyl suberimidate cross-linkers in the ATPase-ATP synthase complex. The OSCP cross-linked products were identified either by immunocharacterization with anti-alpha, anti-beta, or anti-OSCP monoclonal antibodies or by their molecular weight. OSCP was cross-linked with either the alpha- or beta-subunits of F1 or to a subunit of Mr 24 000. Other types of cross-linking were obtained by the labeling of OSCP with [cysteamine-35S]-N-succinimidyl 3-[[2-((2-nitro-4-azidophenyl)amino)ethyl]dithio]propionate ([35S]SNAP) and reconstitution of SNAP-OSCP with F1 in urea-treated submitochondrial particles. Under these conditions, OSCP is found to be adjacent to two other peptides of molecular weight close to 30 000. A comparison is made between the topology and the organization of the b-subunit of Escherichia coli and OSCP, suggesting an analogy between OSCP and the hydrophilic part of the b-subunit.

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“…These results were corroborated and expanded by other authors, who showed that CypD deficiency attenuated ATP synthase dysregulation, restoring bioenergetics, via interaction with the oligomycin-sensitivity conferring protein (OSCP) [ 76 , 78 ]. OSCP is a protein that is located in the peripheral stalk of the ATP synthase, providing structural stability to this enzyme [ 86 ]. While the expression of OSCP has been demonstrated to decrease with aging, the interaction between CypD and OSCP increases with aging, most likely due to the increased expression of CypD [ 77 , 78 ].…”

Section: Atp Synthase Dysfunction In Admentioning

confidence: 99%

ATP Synthase and Mitochondrial Bioenergetics Dysfunction in Alzheimer’s Disease

Patro

Ratna

Yamamoto

et al. 2021

IJMS

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Alzheimer’s Disease (AD) is the most common neurodegenerative disorder in our society, as the population ages, its incidence is expected to increase in the coming decades. The etiopathology of this disease still remains largely unclear, probably because of the highly complex and multifactorial nature of AD. However, the presence of mitochondrial dysfunction has been broadly described in AD neurons and other cellular populations within the brain, in a wide variety of models and organisms, including post-mortem humans. Mitochondria are complex organelles that play a crucial role in a wide range of cellular processes, including bioenergetics. In fact, in mammals, including humans, the main source of cellular ATP is the oxidative phosphorylation (OXPHOS), a process that occurs in the mitochondrial electron transfer chain (ETC). The last enzyme of the ETC, and therefore the ulterior generator of ATP, is the ATP synthase. Interestingly, in mammalian cells, the ATP synthase can also degrade ATP under certain conditions (ATPase), which further illustrates the crucial role of this enzyme in the regulation of cellular bioenergetics and metabolism. In this collaborative review, we aim to summarize the knowledge of the presence of dysregulated ATP synthase, and of other components of mammalian mitochondrial bioenergetics, as an early event in AD. This dysregulation can act as a trigger of the dysfunction of the organelle, which is a clear component in the etiopathology of AD. Consequently, the pharmacological modulation of the ATP synthase could be a potential strategy to prevent mitochondrial dysfunction in AD.

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The oligomycin sensitivity conferring protein (OSCP) of beef heart mitochondria: Studies of its binding to F1 and its function

Cited by 18 publications

References 35 publications

Functional F1-ATPase Essential in Maintaining Growth and Membrane Potential of Human Mitochondrial DNA-depleted ρ° Cells

Functional F1-ATPase Essential in Maintaining Growth and Membrane Potential of Human Mitochondrial DNA-depleted ρ° Cells

Topography of oligomycin sensitivity conferring protein in the mitochondrial adenosine triphosphatase-ATP synthase

ATP Synthase and Mitochondrial Bioenergetics Dysfunction in Alzheimer’s Disease

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