What We Learned From Big Data for Autophagy Research

Abstract

Autophagy is the process by which cytoplasmic components are engulfed in double-membraned vesicles before being delivered to the lysosome to be degraded. Defective autophagy has been linked to a vast array of human pathologies. The molecular mechanism of the autophagic machinery is well-described and has been extensively investigated. However, understanding the global organization of the autophagy system and its integration with other cellular processes remains a challenge. To this end, various bioinformatics and network biology approaches have been developed by researchers in the last few years. Recently, large-scale multi-omics approaches (like genomics, transcriptomics, proteomics, lipidomics, and metabolomics) have been developed and carried out specifically focusing on autophagy, and generating multi-scale data on the related components. In this review, we outline recent applications of in silico investigations and big data analyses of the autophagy process in various biological systems.

Keywords: autophagy; big data; bioinformatics; proteomics; transcriptomics.

Figure 1

Types of autophagy processes. (A) Macroautophagy is induced by the activation of the ULK1 and PI3K-III complexes. Modification of LC3/ATG8 proteins with phosphatidylethanolamine (PE) and anchorage to the membrane of the elongating autophagosome depends on the Atg12-Atg5-Atg16L conjugation system. LC3 can interact with cargoes and selective autophagy receptors via a LIR motif. Enclosed autophagosome eventually fuses with the lysosome for the degradation and recycling of its content. (B) Chaperone-mediated autophagy (CMA) consists in the translocation of proteins into the lysosome through pores formed of LAMP-2A protein stabilized by phosphorylated GFAP. (C) Microautophagy consists in the internalization on cytoplasmic components into the lysosome by direct invagination of the lysosomal membrane. (D) Endosomal-microautophagy depends on the isolation of cytosolic protein in the late endosome before being addressed to the lysosome for degradation. Both CMA and endosomal-microautophagy rely on the chaperone protein Hsc70 that can bind to substrate proteins containing a KFERQ motif.

Figure 2

Studies using multi-omics data to understand autophagy and its regulation. Currently available autophagy-related databases highlighting the different stages of regulation and high-throughput data are shown. TF, Transcription Factor; ARN, Autophagy Regulation Network; GamDB, Gerontology-Autophagic-MicroRNA Database; AD, Autophagy Database; HADB, Human Autophagy Database; THANATOS, THe Autophagy; Necrosis, ApopTosis OrchestratorS.