Acidocalcisome is required for autophagy in<i>Trypanosoma brucei</i>

Li, Feng‐Jun; He, Cynthia Y.

doi:10.4161/auto.36183

Cited by 48 publications

(47 citation statements)

References 56 publications

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“…Another important function demonstrated recently was the involvement of acidocalcisomes in autophagy in T. brucei [71]. Treatment of procyclic stages with bafilomycin A 1 (a V-H + -ATPase inhibitor), monensin (a Na + /H + ionophore), or the combination of NH 4 Cl and ionomycin (alkalinizing agents) inhibited starvation-induced autophagosome formation, suggesting the need for functional acidic organelles for autophagy to occur.…”

Section: Novel Functionsmentioning

confidence: 99%

The origin and evolution of the acidocalcisome and its interactions with other organelles

Docampo

2016

Molecular and Biochemical Parasitology

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Acidocalcisomes are acidic calcium stores that have been found from bacteria to human cells. They are rich in phosphorus compounds in the form of orthophosphate (Pi), pyrophosphate (PPi), and polyphosphate (polyP) and their acidity is maintained by proton pumps such as the vacuolar proton pyrophosphatase (V-H+-PPase, or VP1), the vacuolar proton ATPase (V-H+-ATPase), or both. Recent studies in trypanosomatids and in other species have revealed their role in phosphate metabolism, and cation and water homeostasis, as suggested by the presence of novel pumps, transporters, and channels. An important role in autophagy has also been described. The study of the biogenesis of acidocalcisomes as well as of the interactions of these lysosome-related organelles with other organelles have uncovered important roles in calcium signaling and osmoregulation. Significantly, despite conservation of acidocalcisomes across all of cellular life, there is evidence for intimate integration of these organelles with eukaryotic cellular functions, and which are directly relevant to parasites.

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Section: Novel Functionsmentioning

confidence: 99%

The origin and evolution of the acidocalcisome and its interactions with other organelles

Docampo

2016

Molecular and Biochemical Parasitology

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“…As indicated above the presence of mechanisms for Ca 2+ uptake (Ca 2+ -ATPase) and release (IP 3 R) suggest a role in Ca 2+ signaling [6]. A role in autophagy in T. brucei was recently revealed [43]. Downregulation of components of the AP-3 complex, involved in acidocalcisome biogenesis, inhibits starvation-induced autophagosome formation [43].…”

Section: Introductionmentioning

confidence: 99%

“…A role in autophagy in T. brucei was recently revealed [43]. Downregulation of components of the AP-3 complex, involved in acidocalcisome biogenesis, inhibits starvation-induced autophagosome formation [43]. In T. cruzi, several studies reported the role of acidocalcisomes in osmoregulation.…”

Section: Introductionmentioning

confidence: 99%

Acidocalcisomes of eukaryotes

Docampo

Huang

2016

Current Opinion in Cell Biology

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Acidocalcisomes are organelles rich in polyphosphate and cations and acidified by proton pumps. Although they have also been described in prokaryotes they have been better characterized in unicellular and multicellular eukaryotes. Eukaryotic acidocalcisomes belong to the group of lysosome-related organelles. They have a variety of functions, from the storage of cations and phosphorus to calcium signaling, autophagy, osmoregulation, blood coagulation, and inflammation. Acidocalcisomes of several unicellular eukaryotes possess a variety of transporters, channels and pumps implying a large energetic requirement for their maintenance and suggesting other important functions waiting to be discovered.

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“…The core autophagy events, from double-membraned autophagosome formation to the final degradation in lysosomes are conserved [8], and autophagy-related functions of several ATG homologs or protein complex including ATG3, ATG5, ATG7, ATG24 and PI3K have also been confirmed [8,[13][14]. Interestingly, the acidocalcisomes, a lysosome-related organelle found in trypanosomes and some other protozoan parasites are found to be required for autophagy induction [15]. In higher eukaryotes, the lysosomes are not only involved in the last degradation step of autophagy, but also involved in the induction step through mTOR signaling.…”

Section: Autophagy In T Bruceimentioning

confidence: 95%

Autophagy in Protozoan Parasites: Trypanosoma Brucei as a Model

2017

Future Microbiol.

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" To gain further and more complete understanding of the mechanisms and functions of autophagy, both conserved and evolutionarily divergent, study of more divergent model systems is needed. " Autophagy is an intracellular pathway that clears macromolecules, organelles and intracellular pathogens through autophagosomes and lysosomes upon nutrient limitation, infections and other physiological/pathological conditions. Autophagy has been best studied in budding yeast and mammals, revealing highly conserved machineries and physiological importance in development and diseases. In general, autophagy is triggered upon inhibition of TOR, or activation of AMPK; both conserved protein kinases. Phosphorylation and activation of ATG13 lead to activation of ULK1/2 (Atg1 in yeast), which further stimulates autophagic modules including the PtdIns3K complex: VPS34 and Beclin1, and the unbiquition-like conjugation system that includes ATG8 and ATG12. VPS34 produces PtdIns3P at certain cellular locations, which serves as a signal to recruit other proteins for phagophore formation. The phagophores elongate and engulf cytoplasmic components, forming double-membraned autophagosomes. Finally, autophagosomes are transported to and fused with lysosomes, where the engulfed materials are degraded.Most of the autophagy-related genes identified are highly conserved functionally in yeast and mammals, although different regulatory or signaling mechanisms have been found for some molecules, mTOR as an example [1]. The protozoan parasites are evolutionarily divergent, single-celled eukaryotic pathogens including the Plasmodium spp. that causes malaria; Toxoplasma gondii that causes toxoplasmosis; and Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. that cause the tritryp diseases. Together these pathogens cause huge economic and disease burdens globally. Bioinformatics analysis identified only about half of the ATG homologs in these protozoan parasites [2], implying a simple or divergent autophagy pathway in these organisms. To gain further and more complete understanding of the mechanisms and functions of autophagy, both conserved and evolutionarily divergent, study of more divergent model systems is needed. Advantages of T. brucei as a model organism for cell biology studiesAmong the protozoan parasites, T. brucei is one of the most genetically accessible for study in laboratories. Like many parasites, T. brucei undergoes a complex life cycle in the insect vector and mammalian hosts, taking on different developmental forms. Cultivation and differentiation of some life-cycle stages can be achieved in vitro, making T. brucei an ideal organism to study the signaling and cellular remodeling mechanisms during life-cycle differentiation and development. Advanced reverse genetics methods such as inducible expression [3,4] and RNAi [5] allow rapid characterization of protein functions. Additionally, T. brucei possesses a variety of organelles, ubiquitously found in all eukaryotes or uniquely present in trypanosomes, many of them present at ...

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Acidocalcisome is required for autophagy inTrypanosoma brucei

Cited by 48 publications

References 56 publications

The origin and evolution of the acidocalcisome and its interactions with other organelles

The origin and evolution of the acidocalcisome and its interactions with other organelles

Acidocalcisomes of eukaryotes

Autophagy in Protozoan Parasites: Trypanosoma Brucei as a Model

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