Temporal Partitioning of the Yeast Cellular Network - Systems Biology of Metabolic and Signaling Networks - page 335

Delini-Stula et al. 1988 ). Together with the effects of protonophores (Sect. 12.7 )
through time domains from milliseconds to cell division times (Fig. 12.7 ), it becomes
evident that signalling between timescales is mediated either directly or by the
downstream effects of a number of small effector molecules (H + ,O 2 • ,andH 2 S).
Redox cycles lie close to core of global scale-free cellular dynamics (Rapkine
1931 ; Mano 1977 ; Lloyd and Murray 2005 , 2006 , 2007 ; Lloyd et al. 2012 ). The
significance of scale-free temporal organisation for organelle, cell and organism
timekeeping cannot be overstated as, potentially, what affects one timescale affects
them all: a fundamental property of dynamic fractals (Aon et al. 2008 ).
12.9 Concluding Remarks
“What are called structures are slow processes of long duration, functions are quick
processes of short duration” (von Bertalanffy, Problems of Life 1952 ).
The respiratory oscillation percolates through almost every facet of the biochemis-
try and biology of cellular processes, and although transcription feed-forward
protein feedback loops are important for the regulation and long-term stability of
the oscillation, they do not act in isolation. Current dogma dictates that there is a
distinctive hierarchy in cellular processes where DNA forms RNA to form proteins
that biochemically alter other proteins or produce metabolites; however, biological
networks cannot be so conveniently modularised. Therefore, we must conclude that
real biological networks are heterarchical (where theoretically each sub-system is
of equal importance) rather than hierarchical in their organisation (if a hierarchy
does exist co-factors and co-enzymes would surely take the number one spot). This
viewpoint does not preclude hierarchical structure in the sub-systems that comprise
the heterarchy. Therefore, cell fate is dictated by the integrated output of the
reactome rather than by specific structures in the system. Thus a highly
interconnected reactome responds in a redox-phase-dependent manner, which can
robustly adapt to most perturbative influences.
Our data and observations, although incomplete, provide a compelling picture of
the holistic organisation of yeast. In an autodynamic system, where almost every
facet of cell biology oscillates without external perturbation the concept of cause
and effect is meaningless. Cell physiology is organised so that parallel interlocked
events occur throughout all of the constituents of the system, i.e. macromolecules
(DNA, RNA, proteins, lipids) and small molecules (metabolites, gases), as the
organism adapts to the environmental context. At first glance this would appear
to introduce a high degree of complexity to the system. However, our comparative
study on the 1,327 independent array hybridisations illustrates (Fig. 12.4b )ifa
condition is changed the transcriptome (and presumably its output) locks into either
anabolic or catabolic modes. Furthermore, ATP availability and utilisation is
implicit in the formation of these transcriptional states. ATP synthesis in respiring
cells is a function of the redox potential and the ability of the mitochondria to