Activity and stability of life-supporting proteins are determined not only by their abundance and by post-translational modifications, but also by specific protein-protein interactions. This holds true both for signal-transduction and energy-converting cascades. For vital processes such as life-span control and senescence, to date predominantly age-dependent alterations in abundance and to lesser extent in post-translational modifications of proteins are examined to elucidate the cause of ageing at the molecular level. In mitochondria of rat cortex, we quantified profound changes in the proportion of supramolecular assemblies (supercomplexes) of the respiratory chain complexes I, III(2), IV as well as of the MF(o)F(1) ATP synthase (complex V) by 2D-native/SDS electrophoresis and fluorescent staining. Complex I was present solely in supercomplexes and those lacking complex IV were least stable in aged animals (2.4-fold decline). The ATP synthase was confirmed as a prominent target of age-associated degradation by an overall decline in abundance of 1.5-fold for the monomer and an 2.8-fold increase of unbound F(1). Oligomerisation of the ATP synthase increases during ageing and might modulate the cristae architecture. These data could explain the link between ageing and respiratory control as well as ROS generation.
Copyright (c) 2010 Elsevier Inc. All rights reserved.