English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

The importance of autophagy in parasites with a digenetic life cycle like  Leishmania  spp. is significant. The parasite survives as promastigotes in the insect gut and as immotile amastigotes in mammals. This study demonstrates increased autophagy in  Leishmania  parasite during progression of in vitro life cycle and upon exposure to stress stimuli like starvation, oxidative stress, and drugs. Autophagy inhibition during stress exposure increased cell death, indicating the importance of autophagy in cellular defense against adverse conditions. Atg8 protein, a homolog of mammalian autophagy protein LC3 is expressed in  Leishmania  parasite but its function remains unknown. Overexpression of Atg8 ( Atg8- OE) rendered the parasites resistant to stress and capable of infecting macrophages in substantial numbers; however, disruption of the  Atg8  gene (Δ Atg8 ) resulting in suppression of Atg8 protein expression, increased susceptibility to stress and reduced the capability to cause infection. A critical event in the  Leishmania  parasite lifecycle is the differentiation of promastigote forms to the disease causing amastigote forms. The failure of Δ Atg8  parasites lacking Atg8 protein to differentiate into amastigotes, unlike the  Atg8- OE and vector-transfected parasites, clearly indicated Atg8 involvement in a crucial event. The inability of Δ Atg8  parasites to infect macrophages in vitro was verified in an in vivo mouse model of leishmaniases where infection could not be induced by the Δ Atg8  parasites. Autophagy is known to be involved in the remodeling of damaged organelles. The accumulation of Atg8 around damaged mitochondria suggested increase of autophagy in the vicinity of the organelle. This buildup was prevented when mitochondria generated reactive oxygen species that were quenched, suggesting them as possible signaling molecules for sensing mitochondrial instability. In summary, our study provides new evidences for a crucial role of Atg8 protein in sustaining  Leishmania  parasite survival during life cycle and stress exposure, differentiation to amastigotes, and their infective abilities.

Leishmania donovani parasite requires Atg8 protein for infectivity and survival under stress