Picture of athlete cycling

Open Access research with a real impact on health...

The Strathprints institutional repository is a digital archive of University of Strathclyde's Open Access research outputs. Strathprints provides access to thousands of Open Access research papers by Strathclyde researchers, including by researchers from the Physical Activity for Health Group based within the School of Psychological Sciences & Health. Research here seeks to better understand how and why physical activity improves health, gain a better understanding of the amount, intensity, and type of physical activity needed for health benefits, and evaluate the effect of interventions to promote physical activity.

Explore open research content by Physical Activity for Health...

ATG5 is essential for ATG8-dependent autophagy and mitochondrial homeostasis in Leishmania major

Williams, Roderick A M and Smith, Terry K and Cull, Benjamin and Mottram, Jeremy C and Coombs, Graham H (2012) ATG5 is essential for ATG8-dependent autophagy and mitochondrial homeostasis in Leishmania major. PLOS Pathogens, 8 (5).

[img]
Preview
Other (Williams-etal-PLOSP-2012-ATG5-is-essential-for-ATG8-dependent-autophagy-and-mitochondrial-homeostasis)
Williams_etal_PLOSP_2012_ATG5_is_essential_for_ATG8_dependent_autophagy_and_mitochondrial_homeostasis.PDF - Final Published Version
License: Creative Commons Attribution 4.0 logo

Download (1MB) | Preview

Abstract

Macroautophagy has been shown to be important for the cellular remodelling required for Leishmania differentiation. We now demonstrate that L. major contains a functional ATG12-ATG5 conjugation system, which is required for ATG8-dependent autophagosome formation. Nascent autophagosomes were found commonly associated with the mitochondrion. L. major mutants lacking ATG5 (Δatg5) were viable as promastigotes but were unable to form autophagosomes, had morphological abnormalities including a much reduced flagellum, were less able to differentiate and had greatly reduced virulence to macrophages and mice. Analyses of the lipid metabolome of Δatg5 revealed marked elevation of phosphatidylethanolamines (PE) in comparison to wild type parasites. The Δatg5 mutants also had increased mitochondrial mass but reduced mitochondrial membrane potential and higher levels of reactive oxygen species. These findings indicate that the lack of ATG5 and autophagy leads to perturbation of the phospholipid balance in the mitochondrion, possibly through ablation of membrane use and conjugation of mitochondrial PE to ATG8 for autophagosome biogenesis, resulting in a dysfunctional mitochondrion with impaired oxidative ability and energy generation. The overall result of this is reduced virulence.