Quantitative Analysis of Diubiquitin Isomers Using Ion Mobility-Mass Spectrometry

The diversity of ubiquitin modifications calls for methods to better characterize ubiquitin chain linkage, length, and morphology. Here, we use multiple linear regression analysis coupled with ion mobility mass spectrometry (IM-MS) to quantify the relative abundance of different ubiquitin dimer isomers. We demonstrate the utility and robustness of this approach by quantifying the relative abundance of different ubiquitin dimers in complex mixtures and comparing the results to the standard, bottom-up ubiquitin AQUA method. Our results provide a foundation for using multiple linear regression analysis and IM-MS to characterize more complex ubiquitin chain architectures

On the Role of Normal Aging Processes in the Onset and Pathogenesis of Diseases Associated with the Abnormal Accumulation of Protein Aggregates

Aging is a prime systemic cause of various age-related diseases, in particular, proteinopathies. In fact, most diseases associated with protein misfolding are sporadic, and their incidence increases with aging. This review examines the process of protein aggregate formation, the toxicity of such aggregates, the organization of cellular systems involved in proteostasis, and the impact of protein aggregates on important cellular processes leading to proteinopathies. We also analyze how manifestations of aging (mitochondrial dysfunction, dysfunction of signaling systems, changes in the genome and epigenome) facilitate pathogenesis of various proteinopathies either directly, by increasing the propensity of key proteins for aggregation, or indirectly, through dysregulation of stress responses. Such analysis might help in outlining approaches for treating proteinopathies and extending healthy longevity