Caenorhabditis elegans UCP4 protein controls complex II-mediated oxidative phosphorylation through succinate transport

Matthew Pfeiffer, Ernst Bernhard Kayzer, Xianmei Yang, Ellen Abramson, M. Alexander Kenaston, Cory U. Lago, Herng Hsiang Lo, Margaret M. Sedensky, Adam Lunceford, Catherine F. Clarke, Sarah J. Wu, Chris McLeod, Toren Finkel, Philip G. Morgan, Edward M. Mills

Research output: Contribution to journalArticlepeer-review

Abstract

The novel uncoupling proteins (UCP2-5) are implicated in the mitochondrial control of oxidant production, insulin signaling, and aging. Attempts to understand their functions have been complicated by overlapping expression patterns in most organisms. Caenorhabditis elegans nematodes are unique because they express only one UCP ortholog, ceUCP4 (ucp4). Here, we performed detailed metabolic analyzes in genetically modified nematodes to define the function of the ceUCP4. The knock-out mutant ucp4 (ok195) exhibited sharply decreased mitochondrial succinate- driven (complex II) respiration. However, respiratory coupling and electron transport chain function were normal in ucp4 mitochondria. Surprisingly, isolated ucp4 mitochondria showed markedly decreased succinate uptake. Similarly, ceUCP4 inhibition blocked succinate respiration and import in wild type mitochondria. GeneticandpharmacologicinhibitionofcomplexIfunction was selectively lethal to ucp4 worms, arguing that ceUCP4- regulated succinate transport is required for optimal complex II function in vivo. Additionally, ceUCP4 deficiency prolonged lifespan in the short-lived mev1 mutant that exhibits complex II-generated oxidant production. These results identify a novel function for ceUCP4 in the regulation of complex II-based metabolism through an unexpected mechanism involving succinate transport.

Original languageEnglish (US)
Pages (from-to)37712-37720
Number of pages9
JournalJournal of Biological Chemistry
Volume286
Issue number43
DOIs
StatePublished - Oct 28 2011
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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