Dual function of Sec16B

Tani, Kazuhide; Tagaya, Mitsuo; Yonekawa, Shusuke; Baba, Takashi

doi:10.4161/cl.1.4.18341

Cited by 9 publications

(1 citation statement)

References 41 publications

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“…lipolytica PEX16s are N-glycosylated in the ER, and mutation to ER exit machinery blocks ER exit [ 27 , 50 ]. In human cells, PEX16 ER exit depends on the protein SEC16B [ 61 , 62 ]. TbPEX16 was recently characterized in BSF and PF T .…”

Section: Recent Studies Suggest Glycosomes Can Proliferate De Novo Inmentioning

confidence: 99%

Glycosome biogenesis in trypanosomes and the de novo dilemma

Bauer

Morris

2017

PLoS Negl Trop Dis

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Trypanosomatid parasites, including Trypanosoma and Leishmania, are the causative agents of lethal diseases threatening millions of people around the world. These organisms compartmentalize glycolysis in essential, specialized peroxisomes called glycosomes. Peroxisome proliferation can occur through growth and division of existing organelles and de novo biogenesis from the endoplasmic reticulum. The level that each pathway contributes is debated. Current evidence supports the concerted contribution of both mechanisms in an equilibrium that can vary depending on environmental conditions and metabolic requirements of the cell. Homologs of a number of peroxins, the proteins involved in peroxisome biogenesis and matrix protein import, have been identified in T. brucei. Based on these findings, it is widely accepted that glycosomes proliferate through growth and division of existing organelles; however, to our knowledge, a de novo mechanism of biogenesis has not been directly demonstrated. Here, we review recent findings that provide support for the existence of an endoplasmic reticulum (ER)-derived de novo pathway of glycosome biogenesis in T. brucei. Two studies recently identified PEX13.1, a peroxin involved in matrix protein import, in the ER of procyclic form T. brucei. In other eukaryotes, peroxins including PEX13 have been found in the ER of cells undergoing de novo biogenesis of peroxisomes. In addition, PEX16 and PEX19 have been characterized in T. brucei, both of which are important for de novo biogenesis in other eukaryotes. Because glycosomes are rapidly remodeled via autophagy during life cycle differentiation, de novo biogenesis could provide a method of restoring glycosome populations following turnover. Together, the findings we summarize provide support for the hypothesis that glycosome proliferation occurs through growth and division of pre-existing organelles and de novo biogenesis of new organelles from the ER and that the level each mechanism contributes is influenced by glucose availability.

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Section: Recent Studies Suggest Glycosomes Can Proliferate De Novo Inmentioning

confidence: 99%

Glycosome biogenesis in trypanosomes and the de novo dilemma

Bauer

Morris

2017

PLoS Negl Trop Dis

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Peroxisome Biogenesis

Kawaguchi¹,

Imanaka²

2019

Peroxisomes: Biogenesis, Function, and Role in Human Disease

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Identification and functional characterization of Trypanosoma brucei peroxin 16

Kalel

Schliebs

Erdmann

2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Protozoan parasites of the family Trypanosomatidae infect humans as well as livestock causing devastating diseases like sleeping sickness, Chagas disease, and Leishmaniasis. These parasites compartmentalize glycolytic enzymes within unique organelles, the glycosomes. Glycosomes represent a subclass of peroxisomes and they are essential for the parasite survival. Hence, disruption of glycosome biogenesis is an attractive drug target for these Neglected Tropical Diseases (NTDs). Peroxin 16 (PEX16) plays an essential role in peroxisomal membrane protein targeting and de novo biogenesis of peroxisomes from endoplasmic reticulum (ER). We identified trypanosomal PEX16 based on specific sequence characteristics and demonstrate that it is an integral glycosomal membrane protein of procyclic and bloodstream form trypanosomes. RNAi mediated partial knockdown of Trypanosoma brucei PEX16 in bloodstream form trypanosomes led to severe ATP depletion, motility defects and cell death. Microscopic and biochemical analysis revealed drastic reduction in glycosome number and mislocalization of the glycosomal matrix enzymes to the cytosol. Asymmetry of the localization of the remaining glycosomes was observed with a severe depletion in the posterior part. The results demonstrate that trypanosomal PEX16 is essential for glycosome biogenesis and thereby, provides a potential drug target for sleeping sickness and related diseases.

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Dual function of Sec16B

Cited by 9 publications

References 41 publications

Glycosome biogenesis in trypanosomes and the de novo dilemma

Glycosome biogenesis in trypanosomes and the de novo dilemma

Peroxisome Biogenesis

Identification and functional characterization of Trypanosoma brucei peroxin 16

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