Abstract
Molecular and cellular biology methodology is traditionally based on the reasoning called “the mechanistic explanation”. In practice, this means identifying and selecting correlations between biological processes which result from our manipulation of a biological system. In theory, a successful application of this approach requires precise knowledge about all parameters of a studied system. However, in practice, due to the systems’ complexity, this requirement is rarely, if ever, accomplished. Typically, it is limited to a quantitative or semi-quantitative measurements of selected parameters (e.g., concentrations of some metabolites), and a qualitative or semi-quantitative description of expression/post-translational modifications changes within selected proteins. A quantitative proteomics approach gives a possibility of quantitative characterization of the entire proteome of a biological system, in the context of the titer of proteins as well as their post-translational modifications. This enables not only more accurate testing of novel hypotheses but also provides tools that can be used to verify some of the most fundamental dogmas of modern biology. In this short review, we discuss some of the consequences of using quantitative proteomics to verify several key concepts in skeletal muscle physiology.
Highlights
Traditional approaches to the identification of the role of signaling pathways in regulating cellular behavior most often focus on single components of a studied pathway, without taking into account the full complexity of the pathway, let alone the complexity of a whole cell.Often, within this pathway, the quantity of a studied protein is not referred to quantities of other proteins in the same pathway, or it is just compared under different treatments, or even between different types of cells or tissues
A great variety of proteomic approaches have been developed and they have been employed to investigate the changes in proteomes of normal muscle fibers and muscles affected by pathological conditions such as type 2 diabetes, neuromuscular disorders, age-related sarcopenia and dystrophy [21,38,39,40]
Rather than focusing on a small number of proteins, Mass spectrometry (MS)-based proteomics provides a comprehensive picture of the changes in total protein levels within the muscle fibers
Summary
Traditional approaches to the identification of the role of signaling pathways in regulating cellular behavior most often focus on single components of a studied pathway, without taking into account the full complexity of the pathway (or its relationship with other pathways), let alone the complexity of a whole cell. Focusing on a small number of proteins, usually within one or two pathways, and neglecting other possible interaction partners is not likely to aid the discovery of effective treatments of diseases To achieve this goal, we have to get the all-encompassing view of a cell’s metabolism, and for this, we need to know the full proteome of the cell. Recent evidence suggests that there is a correlation between enzyme titer and its maximal activity, indicating that enzyme concentration is a good proxy for its catalytic potential in vivo [3] In this short review, we discuss the consequences of using a label- and standard-free quantitative proteomics approach to verify several key concepts in skeletal muscle physiology. We conclude that a thorough re-examination of these mechanisms may be necessary before we can profoundly understand muscle physiology and discover new targets for the treatment of muscle disease
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