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Article: Uncoupling protein-4 (UCP4) increases ATP supply by interacting with mitochondrial complex II in neuroblastoma cells

TitleUncoupling protein-4 (UCP4) increases ATP supply by interacting with mitochondrial complex II in neuroblastoma cells
Authors
Issue Date2012
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2012, v. 7 n. 2 How to Cite?
AbstractMitochondrial uncoupling protein-4 (UCP4) protects against Complex I deficiency as induced by 1-methyl-4-phenylpyridinium (MPP +), but how UCP4 affects mitochondrial function is unclear. Here we investigated how UCP4 affects mitochondrial bioenergetics in SH-SY5Y cells. Cells stably overexpressing UCP4 exhibited higher oxygen consumption (10.1%, p<0.01), with 20% greater proton leak than vector controls (p<0.01). Increased ATP supply was observed in UCP4-overexpressing cells compared to controls (p<0.05). Although state 4 and state 3 respiration rates of UCP4-overexpressing and control cells were similar, Complex II activity in UCP4-overexpressing cells was 30% higher (p<0.05), associated with protein binding between UCP4 and Complex II, but not that of either Complex I or IV. Mitochondrial ADP consumption by succinate-induced respiration was 26% higher in UCP4-overexpressing cells, with 20% higher ADP:O ratio (p<0.05). ADP/ATP exchange rate was not altered by UCP4 overexpression, as shown by unchanged mitochondrial ADP uptake activity. UCP4 overexpression retained normal mitochondrial morphology in situ, with similar mitochondrial membrane potential compared to controls. Our findings elucidate how UCP4 overexpression increases ATP synthesis by specifically interacting with Complex II. This highlights a unique role of UCP4 as a potential regulatory target to modulate mitochondrial Complex II and ATP output in preserving existing neurons against energy crisis. © 2012 Ho et al.
Persistent Identifierhttp://hdl.handle.net/10722/145899
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Henry G Leong Professorship in Neurology
Donation Fund for Neurology Research
University of Hong Kong (CRCG, HKU)200901159008
University of Hong Kong
Funding Information:

This project is financially supported by the Henry G Leong Professorship in Neurology (SLH); the Donation Fund for Neurology Research (SLH); Seed Funding for Basic Research, University of Hong Kong (CRCG, HKU 200901159008; PWL Ho). PWL Ho is supported by a Research Assistant Professorship, JWM Ho and HF Liu are supported by a postdoctoral fellowship from the University of Hong Kong. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

 

DC FieldValueLanguage
dc.contributor.authorHo, PWLen_HK
dc.contributor.authorHo, JWMen_HK
dc.contributor.authorTse, HMen_HK
dc.contributor.authorSo, DHFen_HK
dc.contributor.authorYiu, DCWen_HK
dc.contributor.authorLiu, HFen_HK
dc.contributor.authorChan, KHen_HK
dc.contributor.authorKung, MHWen_HK
dc.contributor.authorRamsden, DBen_HK
dc.contributor.authorHo, SLen_HK
dc.date.accessioned2012-03-27T09:01:22Z-
dc.date.available2012-03-27T09:01:22Z-
dc.date.issued2012en_HK
dc.identifier.citationPlos One, 2012, v. 7 n. 2en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/145899-
dc.description.abstractMitochondrial uncoupling protein-4 (UCP4) protects against Complex I deficiency as induced by 1-methyl-4-phenylpyridinium (MPP +), but how UCP4 affects mitochondrial function is unclear. Here we investigated how UCP4 affects mitochondrial bioenergetics in SH-SY5Y cells. Cells stably overexpressing UCP4 exhibited higher oxygen consumption (10.1%, p<0.01), with 20% greater proton leak than vector controls (p<0.01). Increased ATP supply was observed in UCP4-overexpressing cells compared to controls (p<0.05). Although state 4 and state 3 respiration rates of UCP4-overexpressing and control cells were similar, Complex II activity in UCP4-overexpressing cells was 30% higher (p<0.05), associated with protein binding between UCP4 and Complex II, but not that of either Complex I or IV. Mitochondrial ADP consumption by succinate-induced respiration was 26% higher in UCP4-overexpressing cells, with 20% higher ADP:O ratio (p<0.05). ADP/ATP exchange rate was not altered by UCP4 overexpression, as shown by unchanged mitochondrial ADP uptake activity. UCP4 overexpression retained normal mitochondrial morphology in situ, with similar mitochondrial membrane potential compared to controls. Our findings elucidate how UCP4 overexpression increases ATP synthesis by specifically interacting with Complex II. This highlights a unique role of UCP4 as a potential regulatory target to modulate mitochondrial Complex II and ATP output in preserving existing neurons against energy crisis. © 2012 Ho et al.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleUncoupling protein-4 (UCP4) increases ATP supply by interacting with mitochondrial complex II in neuroblastoma cellsen_HK
dc.typeArticleen_HK
dc.identifier.emailHo, SL:slho@hku.hken_HK
dc.identifier.authorityHo, SL=rp00240en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0032810en_HK
dc.identifier.pmid22427795-
dc.identifier.pmcidPMC3303587-
dc.identifier.scopuseid_2-s2.0-84857677363en_HK
dc.identifier.hkuros198928en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84857677363&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume7en_HK
dc.identifier.issue2en_HK
dc.identifier.eissn1932-6203-
dc.identifier.isiWOS:000303003500104-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridHo, PWL=55042444100en_HK
dc.identifier.scopusauthoridHo, JWM=8685214100en_HK
dc.identifier.scopusauthoridTse, HM=55044778100en_HK
dc.identifier.scopusauthoridSo, DHF=55043428500en_HK
dc.identifier.scopusauthoridYiu, DCW=36674071000en_HK
dc.identifier.scopusauthoridLiu, HF=55044244600en_HK
dc.identifier.scopusauthoridChan, KH=36493922700en_HK
dc.identifier.scopusauthoridKung, MHW=36336960300en_HK
dc.identifier.scopusauthoridRamsden, DB=7102612805en_HK
dc.identifier.scopusauthoridHo, SL=25959633500en_HK

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