NDLI: A structured approach to the study of metabolic control principles in intact and impaired mitochondria

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Back cover

Molecular BioSystems Vol - 8 Issue - 2

Molecular BioSystems Vol -7

Molecular BioSystems Vol -6

Molecular BioSystems Vol -5

Molecular BioSystems Vol -4

Molecular BioSystems Vol -3

Molecular BioSystems Vol -2

A structured approach to the study of metabolic control principles in intact and impaired mitochondria

Content Provider	Royal Society of Chemistry (RSC)
Author	Huber, Heinrich J. Dussmann, Heiko Connolly, Niamh M. C. Prehn, Jochen H. M.
Copyright Year	2012
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 (ΔΨm) and, therefore, the protomotive force were critically determined by respiratory complex I activity in healthy mitochondria, complex III activity was dominant for ΔΨm 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.
Starting Page	828
Ending Page	842
Page Count	15
File Format	HTM / HTML PDF
ISSN	1742206X
Volume Number	8
Issue Number	3
Journal	Molecular BioSystems
DOI	10.1039/c2mb05434e
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Mitochondrion Electron transport chain Cytochrome c Bioenergetics Cellular respiration Membrane potential ATP Adenosine triphosphate Cancer
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Biotechnology

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