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A structured approach to the study of metabolic control principles in intact and impaired mitochondria.
Huber, Heinrich J; Connolly, Niamh M C; Dussmann, Heiko; Prehn, Jochen H M.
Afiliação
  • Huber HJ; Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, Dublin 2, Ireland. heinhuber@rcsi.ie
Mol Biosyst ; 8(3): 828-42, 2012 Mar.
Article em En | MEDLINE | ID: mdl-22218564
ABSTRACT
We devised an approach to extract control principles of cellular bioenergetics for intact and impaired mitochondria from ODE-based models and applied it to a recently established bioenergetic model of cancer cells. The approach used two methods for varying ODE model parameters to determine those model components that, either alone or in combination with other components, most decisively regulated bioenergetic state variables. We found that, while polarisation of the mitochondrial membrane potential (ΔΨ(m)) and, therefore, the protomotive force were critically determined by respiratory complex I activity in healthy mitochondria, complex III activity was dominant for ΔΨ(m) during conditions of cytochrome-c deficiency. As a further important result, cellular bioenergetics in healthy, ATP-producing mitochondria was regulated by three parameter clusters that describe (1) mitochondrial respiration, (2) ATP production and consumption and (3) coupling of ATP-production and respiration. These parameter clusters resembled metabolic blocks and their intermediaries from top-down control analyses. However, parameter clusters changed significantly when cells changed from low to high ATP levels or when mitochondria were considered to be impaired by loss of cytochrome-c. This change suggests that the assumption of static metabolic blocks by conventional top-down control analyses is not valid under these conditions. Our approach is complementary to both ODE and top-down control analysis approaches and allows a better insight into cellular bioenergetics and its pathological alterations.
Assuntos

Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Trifosfato de Adenosina / Potencial da Membrana Mitocondrial / Mitocôndrias Tipo de estudo: Prognostic_studies Idioma: En Revista: Mol Biosyst Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Irlanda

Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Trifosfato de Adenosina / Potencial da Membrana Mitocondrial / Mitocôndrias Tipo de estudo: Prognostic_studies Idioma: En Revista: Mol Biosyst Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Irlanda