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Serena Cervantes Evelien M Bunnik Anita Saraf Christopher M Conner Aster Escalante Mihaela E Sardiu Nadia Ponts Jacques Prudhomme Laurence Florens Karine G Le Roch 《Autophagy》2014,10(1):80-92
Autophagy is a catabolic pathway typically induced by nutrient starvation to recycle amino acids, but can also function in removing damaged organelles. In addition, this pathway plays a key role in eukaryotic development. To date, not much is known about the role of autophagy in apicomplexan parasites and more specifically in the human malaria parasite Plasmodium falciparum. Comparative genomic analysis has uncovered some, but not all, orthologs of autophagy-related (ATG) genes in the malaria parasite genome. Here, using a genome-wide in silico analysis, we confirmed that ATG genes whose products are required for vesicle expansion and completion are present, while genes involved in induction of autophagy and cargo packaging are mostly absent. We subsequently focused on the molecular and cellular function of P. falciparum ATG8 (PfATG8), an autophagosome membrane marker and key component of the autophagy pathway, throughout the parasite asexual and sexual erythrocytic stages. In this context, we showed that PfATG8 has a distinct and atypical role in parasite development. PfATG8 localized in the apicoplast and in vesicles throughout the cytosol during parasite development. Immunofluorescence assays of PfATG8 in apicoplast-minus parasites suggest that PfATG8 is involved in apicoplast biogenesis. Furthermore, treatment of parasite cultures with bafilomycin A1 and chloroquine, both lysosomotropic agents that inhibit autophagosome and lysosome fusion, resulted in dramatic morphological changes of the apicoplast, and parasite death. Furthermore, deep proteomic analysis of components associated with PfATG8 indicated that it may possibly be involved in ribophagy and piecemeal microautophagy of the nucleus. Collectively, our data revealed the importance and specificity of the autophagy pathway in the malaria parasite and offer potential novel therapeutic strategies. 相似文献
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Facultative asexual reproduction is a trait commonly found in invasive species. With a
combination of sexual and asexual reproductive modes, such species may adapt to new
environments via sexual recombination during range expansion, while at the same time
having the benefits of asexuality such as the maintenance of fitness effects that depend
upon heterozygosity. In the Western United States, native species of Rubus
(Rosaceae) reproduce sexually whereas exotic naturalized Rubus species reproduce
by pseudogamous apomixis. We hypothesized that new asexual lineages of Rubus
could arise from hybridization in this range. To detect hybridization between native and
exotic Rubus, we genotyped 579 individuals collected across California, Oregon
and Washington with eight nuclear microsatellites and two chloroplast markers. Principal
Coordinate Analysis and Bayesian clustering revealed a limited amount of hybridization of
the native R. ursinus with the exotic R. armeniacus and R.
pensilvanicus, as well as cultivated varieties. Genetic distances between these
hybrids and their offspring indicated that both R. ursinus × R.
armeniacus and R. ursinus × R. pensilvanicus produced a mix
of apomictic and sexual seeds, with sexual seeds being more viable. Although neither of
these hybrid types is currently considered invasive, they model the early stages of
evolution of new invasive lineages, given the potential for fixed heterosis and the
generation of novel genotypes. The hybrids also retain the ability to increase their
fitness via sexual recombination and natural selection. Mixed reproductive systems such as
those described here may be an important step in the evolution of asexual invasive
species. 相似文献
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