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Autophagy in unicellular eukaryotes

Molecular Cell Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, PO Box 14, 9750 Haren, The Netherlands.
Philosophical Transactions of The Royal Society B Biological Sciences (Impact Factor: 6.31). 03/2010; 365(1541):819-30. DOI: 10.1098/rstb.2009.0237
Source: PubMed

ABSTRACT Cells need a constant supply of precursors to enable the production of macromolecules to sustain growth and survival. Unlike metazoans, unicellular eukaryotes depend exclusively on the extracellular medium for this supply. When environmental nutrients become depleted, existing cytoplasmic components will be catabolized by (macro)autophagy in order to re-use building blocks and to support ATP production. In many cases, autophagy takes care of cellular housekeeping to sustain cellular viability. Autophagy encompasses a multitude of related and often highly specific processes that are implicated in both biogenetic and catabolic processes. Recent data indicate that in some unicellular eukaryotes that undergo profound differentiation during their life cycle (e.g. kinetoplastid parasites and amoebes), autophagy is essential for the developmental change that allows the cell to adapt to a new host or form spores. This review summarizes the knowledge on the molecular mechanisms of autophagy as well as the cytoplasm-to-vacuole-targeting pathway, pexophagy, mitophagy, ER-phagy, ribophagy and piecemeal microautophagy of the nucleus, all highly selective forms of autophagy that have first been uncovered in yeast species. Additionally, a detailed analysis will be presented on the state of knowledge on autophagy in non-yeast unicellular eukaryotes with emphasis on the role of this process in differentiation.

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    • "They mentioned the possibility of differences in induction because of the difficulties in the identification of Atg1 orthologs , but did not go into detail . Kiel ( 2010 ) 3 reviewed the available information on autophagy in non - yeast unicellular eukaryotes and focuses on kinetoplastids and Dyctiostelium . Duszenko et al . "
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    ABSTRACT: Autophagy, the lysosome-mediated self-degradation process, is implicated in survival during starvation in yeast, Dictyostelium and animals. In these eukaryotic taxa (collectively called Unikonts), autophagy is induced primarily through the Atg1/ULK1 complex in response to nutrient depletion. Autophagy has also been well-studied in non-unikont parasites, such as Trypanosoma and Plasmodium, and found important in their life-cycle transitions. However, how autophagy is induced in non-unikonts remains largely unrevealed. Using a bioinformatics approach, we examined the presence of Atg1 and of its complex in the genomes of 40 non-unikonts. We found that these genomes do not encode typical Atg1 proteins: BLAST and HMMER queries matched only with the kinase domain of Atg1, while other segments responsible for regulation and protein-binding were missing. Non-unikonts also lacked other components of the Atg1-inducing complex. Orthologs of an alternative autophagy inducer, Atg6 were found only in the half of the species, indicating that the other half may possess other inducing mechanisms. As key autophagy genes have differential expression patterns during life-cycle, we raise the possibility that autophagy in these protists is induced mainly at the post-transcriptional level. Understanding Atg1-independent autophagy induction mechanisms in these parasites may lead to novel pharmacological interventions, not affecting human Atg1-dependent autophagy.
    Scientific Reports 07/2014; 4:5829. DOI:10.1038/srep05829 · 5.58 Impact Factor
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    • "Autophagy is a physiological self-degradative pathway essential for the maintenance of the metabolic balance in eukaryotes, leading to the turnover of cellular structures during both the normal cell cycle and during conditions of stress, such as starvation [21] [22]. This process depends on double-membrane vesicles known as autophagosomes, which are responsible for the engulfment of macromolecules and organelles and the recycling of their components without an inflammatory response [23]. "
    06/2013: chapter Autophagic Balance Between Mammals and Protozoa: A Molecular, Biochemical and Morphological Review of Apicomplexa and Trypanosomatidae Infections;
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    • "A population of acidic vesicles has previously been identified in metacyclic Leishmania which result from macroautophagy , recently shown to be an essential requirement for metacyclogenesis and parasite virulence (Besteiro et al., 2006; 2007). During parasite differentiation , the multivesicular body (MVB)-like network found in multiplicative procyclic parasites matures into a lysosomal-like structure of high lytic capacity and low pH in metacyclic parasites (Besteiro et al., 2006), correlating with the appearance of autophagosomes expressing autophagy-related gene 8 (ATG8), the ubiquitin-like protein required for vesicle formation in yeast (reviewed in Kiel, 2010). To investigate whether the additional vesicles visualized with HASPB18–GFP C3S were autophagosomes , HASPB–GFP parasites were transfected with RFP-ATG8, an N-terminal red fluorescence protein reporter in fusion with the autophagic marker protein, ATG8 (Besteiro et al., 2006; Williams et al., 2006). "
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    ABSTRACT: Proteins of the Leishmania hydrophilic acylated surface protein B (HASPB) family are only expressed in infective parasites (both extra- and intracellular stages) and, together with the peripheral membrane protein SHERP (small hydrophilic endoplasmic reticulum-associated protein), are essential for parasite differentiation (metacyclogenesis) in the sand fly vector. HASPB is a 'non-classically' secreted protein, requiring N-terminal acylation for trafficking to and exposure on the plasma membrane. Here, we use live cell imaging methods to further explore this pathway to the membrane and flagellum. Unlike HASPB trafficking in transfected mammalian cells, we find no evidence for a phosphorylation-regulated recycling pathway in metacyclic parasites. Once at the plasma membrane, HASPB18-GFP (green fluorescent protein) can undergo bidirectional movement within the inner leaflet of the membrane and on the flagellum. Transfer of fluorescent protein between the flagellum and the plasma membrane is compromised, however, suggesting the presence of a diffusion barrier at the base of the Leishmania flagellum. Full-length HASPB is released from the metacyclic parasite surface on to macrophages during phagocytosis but while expression is maintained in intracellular amastigotes, HASPB cannot be detected on the external surface in these cells. Thus HASPB may be a dual function protein that is shed by the infective metacyclic but retained internally once Leishmania are taken up by macrophages.
    Cellular Microbiology 01/2012; 14(5):740-61. DOI:10.1111/j.1462-5822.2012.01756.x · 4.82 Impact Factor
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