ATG24 Represses Autophagy and Differentiation and Is Essential for Homeostasy of the Flagellar Pocket in <i>Trypanosoma brucei</i>



Brennand, Ana, Rico, Eva, Rigden, Daniel J ORCID: 0000-0002-7565-8937, Van Der Smissen, Patrick, Courtoy, Pierre J and Michels, Paul AM
(2015) ATG24 Represses Autophagy and Differentiation and Is Essential for Homeostasy of the Flagellar Pocket in <i>Trypanosoma brucei</i>. PLOS ONE, 10 (6). e0130365-.

[img] Text
Brennand PLoS One 2015.pdf - Unspecified

Download (5MB)
[img] Atom XML (admin)
2017-05-12T11:19:20Z.atom - Unspecified

Download (0B)
[img] Atom XML (admin)
2017-05-12T12:18:17Z.atom - Unspecified

Download (0B)
[img] Atom XML (admin)
2017-05-12T13:17:42Z.atom - Unspecified

Download (0B)
[img] Atom XML (admin)
2017-05-12T14:17:32Z.atom - Unspecified

Download (0B)
[img] Atom XML (admin)
2017-05-12T15:17:43Z.atom - Unspecified

Download (0B)
[img] Atom XML (admin)
2017-05-12T16:17:55Z.atom - Unspecified

Download (0B)
[img] Atom XML (admin)
2017-05-12T17:17:37Z.atom - Unspecified

Download (0B)
[img] Atom XML (admin)
2017-05-12T18:18:03Z.atom - Unspecified

Download (0B)
[img] Atom XML (admin)
2017-05-12T19:17:51Z.atom - Unspecified

Download (0B)
[img] Atom XML (admin)
2017-05-12T20:17:54Z.atom - Unspecified

Download (0B)
[img] Atom XML (admin)
2017-05-12T21:18:12Z.atom - Unspecified

Download (0B)
[img] Atom XML (admin)
2017-05-12T22:18:51Z.atom - Unspecified

Download (0B)
[img] Atom XML (admin)
2017-05-12T23:23:30Z.atom - Unspecified

Download (0B)
[img] Atom XML (admin)
2017-05-13T01:18:59Z.atom - Unspecified

Download (0B)
[img] Atom XML (admin)
2017-05-13T02:18:36Z.atom - Unspecified

Download (0B)
[img] Atom XML (admin)
2017-05-13T03:18:42Z.atom - Unspecified

Download (0B)
[img] Atom XML (admin)
2017-05-13T04:34:10Z.atom - Unspecified

Download (0B)
[img] Atom XML (admin)
2017-05-13T05:18:29Z.atom - Unspecified

Download (0B)
[img] Atom XML (admin)
2017-05-13T06:17:54Z.atom - Unspecified

Download (0B)
[img] Atom XML (admin)
2017-05-13T07:18:18Z.atom - Unspecified

Download (0B)
[img] Atom XML (admin)
2017-05-13T08:18:34Z.atom - Unspecified

Download (0B)
[img] Atom XML (admin)
2017-05-13T09:17:47Z.atom - Unspecified

Download (0B)

Abstract

We have previously identified homologs for nearly half of the approximately 30 known yeast Atg's in the genome database of the human sleeping sickness parasite Trypanosoma brucei. So far, only a few of these homologs have their role in autophagy experimentally confirmed. Among the candidates was the ortholog of Atg24 that is involved in pexophagy in yeast. In T. brucei, the peroxisome-like organelles named glycosomes harbor core metabolic processes, especially glycolysis. In the autotrophic yeast, autophagy is essential for adaptation to different nutritional environments by participating in the renewal of the peroxisome population. We hypothesized that autophagic turnover of the parasite's glycosomes plays a role in differentiation during its life cycle, which demands adaptation to different host environments and associated dramatic changes in nutritional conditions. We therefore characterized T. brucei ATG24, the T. brucei ortholog of yeast Atg24 and mammalian SNX4, and found it to have a regulatory role in autophagy and differentiation as well as endocytic trafficking. ATG24 partially localized on endocytic membranes where it was recruited via PI3-kinase III/VPS34. ATG24 silencing severely impaired receptor-mediated endocytosis of transferrin, but not adsorptive uptake of a lectin, and caused a major enlargement of the flagellar pocket. ATG24 silencing approximately doubled the number of autophagosomes, suggesting a role in repressing autophagy, and strongly accelerated differentiation, in accordance with a role of autophagy in parasite differentiation. Overexpression of the two isoforms of T. brucei ATG8 fused to GFP slowed down differentiation, possibly by a dominant-negative effect. This was overcome by ATG24 depletion, further supporting its regulatory role.

Item Type: Article
Uncontrolled Keywords: Flagella, Endosomes, Trypanosoma brucei brucei, Protozoan Proteins, Endocytosis, Amino Acid Sequence, Conserved Sequence, Sequence Homology, Amino Acid, Protein Transport, Homeostasis, Molecular Sequence Data, Autophagy, Class III Phosphatidylinositol 3-Kinases
Depositing User: Symplectic Admin
Date Deposited: 30 Jun 2015 08:04
Last Modified: 05 Oct 2023 09:26
DOI: 10.1371/journal.pone.0130365
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/2015059