Divide and Conquer

Abstract

Chronic heart failure is a worldwide cause of mortality and morbidity and is the final outcome of a number of different etiologies. This reflects both the complexity of the disease and our incomplete understanding of its underlying molecular mechanisms. One experimental approach to address this is to study subcellular organelles and how their functions are activated and synchronized under physiological and pathological conditions. In this review, we discuss the application of proteomic technologies to organelles and how this has deepened our perception of the cellular proteome and its alterations with heart failure. The use of proteomics to monitor protein quantity and post-translational modifications (PTMs) has revealed a highly intricate and sophisticated level of protein regulation. PTMs have the potential to regulate organelle function and interplay most likely by targeting both structural and signaling proteins throughout the cell, ultimately coordinating their responses. The potentials and limitations of current proteomic technologies are also discussed emphasizing that the development of novel methods will enhance our ability to further investigate organelles and decode intracellular communication.

Novel large-particle FACS purification of adult ventricular myocytes reveals accumulation of myosin and actin disproportionate to cell size and proteome in normal post-weaning development

“…Whole tissue preparations offer at best a “bulk sum” of all proteins from MCs, NMCs, and ECM that may mask cell-type specific changes. Single-cell analysis is preferred to limit proteome redundancy where global and/or specific proteins arise from multiple cell types or ECM 2,3 .…”

Characterization, Design, and Function of the Mitochondrial Proteome: From Organs to Organisms

“…58 The recent demonstration of transcript-level clustering recapitulates the phylogeny of mammalian lineages and supports the notability of expression levels in adaptation. 59 Interestingly, protein abundance, as calculated using NSAF values, varied according to their primary functions across the model systems.…”

High-Resolution Separation of Cardiovascular Proteomes

“…Therefore, enrichment of subproteomes is a highly diverse field of research and would require multiple reviews to be comprehensive. [48][49][50][51][52] Approaches for enrichment are highly versatile ranging from purification of protein complexes (including co-immunoprecipitation) to enrichment according to functional groups (eg, phosphorylation) or subcellular localization (eg, mitochondria; Table). As these proteins are consequently associated with a more or less specific function that is linked to the enriched fraction, the term functional proteomics evolved within this area of research.…”