Arya, H. | bioRxiv Science

bioRxiv2023

PEX1 is essential for the glycosome biogenesis and trypanosomatid parasite survival.

Trypanosomatid parasites are kinetoplastid protists that compartmentalize glycolytic enzymes in unique peroxisome-related organelles called glycosomes. The heterohexameric AAA-ATPase complex of PEX1-PEX6 is anchored to the peroxisomal membrane and functions in the export of matrix protein import receptor PEX5 from the peroxisomal membrane. Defects in PEX1, PEX6 or their membrane anchor causes dysfunction of peroxisomal matrix protein import cycle. In this study, we identified the Trypanosoma PEX1 orthologue using sequence and structural similarities. Using yeast two-hybrid analysis, we demonstrate that TbPEX1 can bind to TbPEX6. Endogenously tagged TbPEX1 localizes to glycosomes in the T. brucei parasites. Depletion of PEX1 gene expression by RNA interference causes lethality to bloodstream form trypanosomes, due to a partial mislocalization of glycosomal enzymes to the cytosol and ATP depletion. TbPEX1 RNAi leads to a selective proteasomal degradation of both matrix protein import receptors TbPEX5 and TbPEX7. Unlike in yeast, PEX1 depletion did not result in an accumulation of ubiquitinated TbPEX5 in trypanosomes. As PEX1 turned out to be essential for trypanosomatid parasites, it could provide a suitable drug target for parasitic diseases. The results also suggests that these parasites possess a highly efficient quality control mechanisms that export the import receptors from glycosomes to the cytosol, in the absence of a functional TbPEX1-TbPEX6 complex.

cell biology↗

bioRxiv2022

Tropical high-altitude insects show limited capacity to handle high temperatures

Growing summer season and increased anthropogenic activities pose a continual challenge to resident species. Ectotherms like insects are especially vulnerable to rapid climatic changes. High-altitude tropical insect populations have been rarely examined for their responses to high-temperature. We exposed a tropical out-bred highland population of Drosophila melanogaster from the Himalayas to growing summer conditions in outdoor mesocosm units. Population response to thermal changes was tracked over ninety days at both phenotypic and genotypic level. Whole genomic resequencing data suggested a clear seasonal shift in allele frequencies. Interestingly, the general heat responsive genes were missing in the summer due to monsoon allele shift; an atypical response noted for high-altitude tropical populations. Instead, candidates involved in kinases and phosphorylation emerged as key players. Heat-knockdown time decreased over time indicating a limited ability to handle increasing temperature. Merging data from both allelic shifts and heat-knockdown time indicated a limited capacity for high-altitude insects in coping with climate warming.

evolutionary biology↗