Comparative bioinformatics analyses and profiling of lysosome-related organelle proteomes

Abstract

Complete and accurate profiling of cellular organelle proteomes, while challenging, is important for the understanding of detailed cellular processes at the organelle level. Mass spectrometry technologies coupled with bioinformatics analysis provide an effective approach for protein identification and functional interpretation of organelle proteomes. In this study, we have compiled human organelle reference datasets from large-scale proteomic studies and protein databases for 7 lysosome-related organelles (LROs), as well as the endoplasmic reticulum and mitochondria, for comparative organelle proteome analysis. Heterogeneous sources of human organelle proteins and rodent homologs are mapped to human UniProtKB protein entries based on ID and/or peptide mappings, followed by functional annotation and categorization using the iProXpress proteomic expression analysis system. Cataloging organelle proteomes allows close examination of both shared and unique proteins among various LROs and reveals their functional relevance. The proteomic comparisons show that LROs are a closely related family of organelles. The shared proteins indicate the dynamic and hybrid nature of LROs, while the unique transmembrane proteins may represent additional candidate marker proteins for LROs. This comparative analysis, therefore, provides a basis for hypothesis formulation and experimental validation of organelle proteins and their functional roles.

Systems biology of the autophagy-lysosomal pathway

“…As a first step in examining the functional and regulatory interactions modulating the autophagy-lysosomal pathway, we compiled relevant genes from the established databases, including Gene Ontology, 27 an autophagy database (http://autophagy.lu), KEGG pathways 28 and literature 3,8,29,30 for both human and murine data. This resulted in a total of 416 genes that included 38 genes with functions in autophagy, 161 autophagy regulators, 64 genes with a role in the lysosomal function or pathways, and 167 lysosomal regulators (Sup.…”

“…The compiled lists were further enhanced by manual curation of published literature. 3,8,29,30 The final list comprises 38 autophagy genes, 161 autophagy regulator genes, 64 lysosomal genes and 167 lysosome regulator genes. Although these gene lists may not be exhaustive and extensive, we reasoned that they represented the best available current knowledge related to autophagy and lysosome regulation in the mammals and can provide key insights into the biology of autophagy-lysosomal pathway.…”

The Regulation of Skin Pigmentation

“…Many of those genes (Ͼ25 at latest count) affect the biogenesis or function of melanosomes, the discrete membranebound organelles within which melanins are synthesized. Melanosomes, which are closely related to lysosomes and are within the family of lysosome-related organelles (LROs), 3 require a number of specific enzymatic and structural proteins to mature and become competent to produce melanin (10,11). As space does not allow a full consideration of melanosome biogenesis and the specific functions of melanosomal proteins, readers are referred to several recent reviews on this topic (12,13).…”

Modifying skin pigmentation – approaches through intrinsic biochemistry and exogenous agents

“…Many genes (>25) regulate melanosomal biogenesis or function, which requires a number of specific enzymatic and structural proteins for effective melanin production [8,9].…”