Journal of Bioenergetics and Biomembranes

, Volume 34, Issue 5, pp 389–395 | Cite as

Role of Copper in Mitochondrial Biogenesis Via Interaction with ATP Synthase and Cytochrome c Oxidase

  • Denis M. MedeirosEmail author
  • Dianne Jennings


Animals that are copper deficient have cardiac hypertrophy where there is a dramatic increase in mitochondria. Mitochondrial biogenesis is enhanced in this model and there is an upregulation of mitochondrial transcription factor A (mtTFA) and nuclear respiratory factors 1 and 2 (NRF-1 and NRF-2). While the cuproenzyme, cytochrome c oxidase (CCO), is an attractive candidate to explain the connection between cardiac hypertrophy in copper deficiency and subsequent mitochondrial biogenesis, studies have revealed that ATP synthase may be impacted by copper depletion. NRF-1 and NRF-2 can bind to some of the subunits of both CCO and ATP synthase to regulate gene expression. Furthermore, oxidative phosphorylation appears to occur unaltered in the copper-deficient state. Copper-deficient mitochondria appear to be less sensitive to the inhibitory effect of oligomycin compared to controls. Decreases in the δ subunit protein and β mRNA transcript have been reported for ATP synthase as a function of copper deficiency. The limited data available suggest that copper, either indirectly or directly, alters ATP synthase function.

ATP synthase copper cytochrome c oxidase mitochondrial transcriptional factor A nuclear respiratory factors mitochondria 


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Copyright information

© Plenum Publishing Corporation 2002

Authors and Affiliations

  1. 1.Department of Human NutritionKansas State UniversityManhattan

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