INA complex liaises the F1Fo-ATP synthase membrane motor modules

Naumenko, Nataliia; Morgenstern, Marcel; Rucktäschel, Robert; Warscheid, Bettina; Rehling, Peter

doi:10.1038/s41467-017-01437-z

Cited by 25 publications

(38 citation statements)

References 45 publications

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“…Human Mitochondria Devoid of Assembled ATP Synthase. Yeast ATP synthase is assembled from preformed modules of the F 1 domain, the peripheral stalk, and the c 10 ring (26,27). The process of assembly of the human enzyme is similar, but not identical (25), and the assembly of its F 1 domain has not been studied in detail yet.…”

Section: Resultsmentioning

confidence: 99%

Persistence of the permeability transition pore in human mitochondria devoid of an assembled ATP synthase

Carroll

Ding

et al. 2019

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

110

106

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The opening of the permeability transition pore, a nonspecific channel in inner mitochondrial membranes, is triggered by an elevated total concentration of calcium ions in the mitochondrial matrix, leading to disruption of the inner membrane and necrotic cell death. Cyclosporin A inhibits pore opening by binding to cyclophilin D, which interacts with the pore. It has been proposed that the pore is associated with the ATP synthase complex. Previously, we confirmed an earlier observation that the pore survives in cells lacking membrane subunits ATP6 and ATP8 of ATP synthase, and in other cells lacking the enzyme’s c8rotor ring or, separately, its peripheral stalk subunits b and oligomycin sensitive conferral protein. Here, we investigated whether the pore is associated with the remaining membrane subunits of the enzyme. Individual deletion of subunits e, f, g, and 6.8-kDa proteolipid disrupts dimerization of the complex, and deletion of DAPIT (diabetes-associated protein in insulin sensitive tissue) possibly influences oligomerization of dimers, but removal of each subunit had no effect on the pore. Also, we removed together the enzyme’s membrane bound c8ring and the δ-subunit from the catalytic domain. The resulting cells assemble only a subcomplex derived from the peripheral stalk and membrane-associated proteins. Despite diminished levels of respiratory complexes, these cells generate a membrane potential to support uptake of calcium into the mitochondria, leading to pore opening, and retention of its characteristic properties. It is most unlikely that the ATP synthase, dimer or monomer, or any component, provides the permeability transition pore.

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Section: Resultsmentioning

confidence: 99%

Persistence of the permeability transition pore in human mitochondria devoid of an assembled ATP synthase

Carroll

Ding

et al. 2019

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

110

106

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“…Ten Atp9 subunits form the F o rotor domain. The association of the F o rotor domain with Atp6 leads to the formation of the proton-conducting channel (Stock et al 1999) and represents a critical step in the assembly of the ATP synthase (Rak et al 2011;Naumenko et al 2017). According to current models, formation of the proton-conducting channel of ATP synthase occurs in intermediate forms that contain the F 1 domain and periph-eral stalk to prevent unimpeded proton leakage across the inner membrane.…”

Section: Atp Synthasementioning

confidence: 99%

“…Future experimental work has to provide insights into the molecular mechanism by which Smt1 regulates translation of the ATP6/ ATP8 mRNA. The INA complex promotes the final formation of the proton-conducting channel by assembling the F o rotor domain with an Atp6/Atp8-containing module of the ATP synthase (Naumenko et al 2017). Interestingly, in the absence of the INA complex, the in organello synthesis of Atp9 is reduced (Naumenko et al 2017).…”

Section: Atp Synthasementioning

confidence: 99%

“…The INA complex promotes the final formation of the proton-conducting channel by assembling the F o rotor domain with an Atp6/Atp8-containing module of the ATP synthase (Naumenko et al 2017). Interestingly, in the absence of the INA complex, the in organello synthesis of Atp9 is reduced (Naumenko et al 2017). Whether a molecular switch exists that controls the translation of ATP9 mRNA in response to the assembly stage of the ATP synthase remains to be investigated.…”

Section: Atp Synthasementioning

confidence: 99%

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Pathways to balance mitochondrial translation and protein import

Priesnitz

Becker

2018

Genes Dev.

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Cytochrome bc 1 complex COB Cbs1 Acts on the 5 ′ untranslated region (UTR) of COB mRNA Associates with mitoribosomes Cbs2 Acts on the 5 ′ UTR of COB mRNA Associates with mitoribosomes Cbp1 Acts on the 5 ′ UTR of COB mRNA Stabilizes COB mRNA Cbp3 Forms a complex with Cpb6 Cbp6 Associates with mitoribosomes Couples translation of COB mRNA with assembly of the cytochrome bc 1 complex Cytochrome c oxidase COX1 Mss51 Acts on the 5 ′ UTR of COX1 mRNA Couples translation of COX1 mRNA with assembly of cytochrome c oxidase Pet309 Binds to COX1 mRNA Stabilizes COX1 mRNA Mam33 Translational activator during fermentative growth Unknown molecular function COX2 Pet111 Acts on the 5 ′ UTR of COX2 mRNA COX3 Pet54 Pet54/Pet122/Pet494 form a complex Pet122 Acts on the 5 ′ UTR of COX3 mRNA Pet494 ATP synthase ATP6 Atp22 Unknown function ATP6/ATP8 Smt1 Translational repressor Binds ATP6/ATP8 mRNA ATP9 Aep1 Unknown function Aep2 Acts on 5 ′ UTR of ATP9 mRNA Atp25 Stabilization of ATP9 mRNA Promotes assembly of Atp9 ring Mitoribosome VAR1 Sov1 Unknown function Protein-encoding mitochondrial genes and their translational regulators in S. cerevisiae are listed. Smt1 acts as translational repressor, while all other translation regulators activate the expression of their target genes.

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“…The other subunits, produced from nuclear genes, are translated in the cellular cytoplasm, imported into the organelle, and assembled together with ATP6 and ATP8 to produce the complete ATP synthase. Although the assembly of the yeast ATP synthase has been studied extensively (5,6), until recently, relatively little was known about how human ATP synthase is assembled. However, gene editing now permits removal of individual subunits of the human enzyme and the subsequent examination of the consequences for assembly.…”

mentioning

confidence: 99%

Assembly of the membrane domain of ATP synthase in human mitochondria

Ford

Carroll

et al. 2018

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

163

182

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The ATP synthase in human mitochondria is a membrane-bound assembly of 29 proteins of 18 kinds. All but two membrane components are encoded in nuclear genes, synthesized on cytoplasmic ribosomes, and imported into the matrix of the organelle, where they are assembled into the complex with ATP6 and ATP8, the products of overlapping genes in mitochondrial DNA. Disruption of individual human genes for the nuclear-encoded subunits in the membrane portion of the enzyme leads to the formation of intermediate vestigial ATPase complexes that provide a description of the pathway of assembly of the membrane domain. The key intermediate complex consists of the F-c complex inhibited by the ATPase inhibitor protein IF and attached to the peripheral stalk, with subunits e, f, and g associated with the membrane domain of the peripheral stalk. This intermediate provides the template for insertion of ATP6 and ATP8, which are synthesized on mitochondrial ribosomes. Their association with the complex is stabilized by addition of the 6.8 proteolipid, and the complex is coupled to ATP synthesis at this point. A structure of the dimeric yeast F membrane domain is consistent with this model of assembly. The human 6.8 proteolipid (yeast j subunit) locks ATP6 and ATP8 into the membrane assembly, and the monomeric complexes then dimerize via interactions between ATP6 subunits and between 6.8 proteolipids (j subunits). The dimers are linked together back-to-face by DAPIT (diabetes-associated protein in insulin-sensitive tissue; yeast subunit k), forming long oligomers along the edges of the cristae.

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INA complex liaises the F1Fo-ATP synthase membrane motor modules

Cited by 25 publications

References 45 publications

Persistence of the permeability transition pore in human mitochondria devoid of an assembled ATP synthase

Persistence of the permeability transition pore in human mitochondria devoid of an assembled ATP synthase

Pathways to balance mitochondrial translation and protein import

Assembly of the membrane domain of ATP synthase in human mitochondria

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