Dictyostelium discoideum and autophagy – a perfect pair

Abstract

Autophagy is subdivided into chaperone-mediated autophagy, microautophagy and macroautophagy and is a highly conserved intracellular degradative pathway. It is crucial for cellular homeostasis and also serves as a response to different stresses. Here we focus on macroautophagy, which targets damaged organelles and large protein assemblies, as well as pathogenic intracellular microbes for destruction. During this process, cytosolic material becomes enclosed in newly generated double-membrane vesicles, the so-called autophagosomes. Upon maturation, the autophagosome fuses with the lysosome for degradation of the cargo. The basic molecular machinery that controls macroautophagy works in a sequential order and consists of the ATG1 complex, the PtdIns3K complex, the membrane delivery system, two ubiquitin-like conjugation systems, and autophagy adaptors and receptors. Since the different stages of macroautophagy from initiation to final degradation of cargo are tightly regulated and highly conserved across eukaryotes, simple model organisms in combination with a wide range of techniques contributed significantly to advance our understanding of this complex dynamic process. Here, we present the social amoeba Dictyostelium discoideum as an advantageous and relevant experimental model system for the analysis of macroautophagy.KEY WORDS: autophagy, ubiquitin-proteasome system (UPS), LC3-associated phagocytosis, proteaphagy Int. J. Dev. Biol. 63: 485-495 (2019)

Functional Characterisation of the Autophagy ATG12~5/16 Complex in Dictyostelium discoideum

“…The formation of autophagosomes has also been observed in the absence of ATG5, ATG3 or ATG7 in MEFs and of all six ATG8 family members in HeLa cells [79][80][81][82][83]. Thus, ATG5, ATG12, ATG16 and the other components of the two ubiquitin-like conjugation systems are less important for autophagosome formation but are critical for efficient autophagosome lysosome fusion and degradation of the inner autophagosomal membrane and the cargo [9,39,82,84].…”

A Dictyostelium model for BPAN disease reveals a functional relationship between the WDR45/WIPI4 homolog Wdr45l and Vmp1 in the regulation of autophagy-associated PtdIns3P and ER stress

“…The autophagic machinery is very well conserved in all eukaryotes including Dictyostelium discoideum, a social amoeba that is gaining importance in the study of the basic mechanisms of human diseases. The autophagy pathway in Dictyostelium and mammalian cells is remarkably similar [46][47][48][49][50][51][52][53][54][55][56][57][58][59]. Here we investigate the consequence of the deletion of the two PROPPIN genes in Dictyostelium and study in more detail Wdr45l, the protein most similar to human WDR45.…”

Proteins in Autophagic Machinery

“…One conclusion of this comparative study is that although proteins of the autophagic machinery have been partially conserved in protists, a clear reduction is observed in parasitic protists, which may be a consequence of specific adaptations to a parasitic life [9]. A clear example is the reduction observed in the parasitic amoeba E. histolytica compared to the non-pathogenic amoeba D. discoideum [10]. Interestingly, the least conserved proteins are those of the ATG1 complex.…”