Legionella pneumophila multiplication is enhanced by chronic AMPK signalling in mitochondrially diseased Dictyostelium cells

Abstract

There was an error in the first ePress version of the article Dis. Model. Mech. 2, 479-489.In the ePress version of 28 July 2009, the Clinical issue section of the Translational Impact text had a missing word, which altered the meaning. The correct sentence should read: 'In many cases, the precise genetic defect causing mitochondrial dysfunction is known, but the downstream pathological outcomes for the mitochondrially diseased cell remain poorly understood. ' The correct version was published on ePress on 30 July 2009. The print version is correct.We apologise for this mistake.

The Dictyostelium model for mitochondrial biology and disease

“…Further investigation of heteroplasmic mitochondrial mutations in D. discoideum revealed that a common phenotypic signature was shared across strains (Francione, 2008, Wilczynska et al, 1997. This signature phenotype includes impaired growth, both on bacterial lawns and in liquid media, deranged phototaxis and thermotaxis, defective multicellular morphogenesis with shortened and thickened fruiting body stalks, and susceptibility to Legionella proliferation within the amoeba (Francione et al, 2009). Interestingly, the antisense inhibition of the D. discoideum chaperonin 60 gene, a protein required for the correct folding of proteins within mitochondria, caused the same aberrant phenotypes (Bokko et al, 2007).…”

“…The depletion of ATP would cause disease through disruption of cellular activities, and those activities/tissues with high energy requirements would be most affected. However, it has been shown in D. discoideum, that mitochondrial disease phenotypes in these cases are attributable to chronic AMP-activated protein kinase (AMPK) signalling rather the direct result of ATP insufficiency (Bokko et al, 2007, Francione et al, 2009. AMPK is an energy-sensing protein kinase responsible for maintaining ATP homeostasis by inhibiting anabolic processes, such as growth and proliferation, and promoting ATP-generating pathways, such as mitochondrial biogenesis and fatty acid oxidation.…”

Interactions and Cytotoxicity of Human Neurodegeneration- Associated Proteins Tau and α-Synuclein in the Simple Model Dictyostelium discoideum

“…Legionella pneumophila infection and proliferation rates in D. discoideum was measured as previously described ( Francione et al, 2009 ) and was adapted from Hagele et al (2000) and Otto et al (2004) . Wildtype and transformant strains were grown to exponential phase axenically in HL5 at 25°C with shaking.…”

“…Among these phenotypes were: decreased growth on bacterial lawns and in axenic medium, aberrant fruiting body with shorter and thicker stalks, defective slug phototaxis and increased susceptibility to Legionella proliferation. These mitochondrially diseased D. discoideum phenotypes were attributed to the chronic activation of the energy sensing protein AMP-activated protein kinase (AMPK) by Bokko et al (2007) and Francione et al (2009) that showed when AMPK was knocked down by antisense inhibition, the defective phenotypes returned to wildtype levels, and chronic activation of AMPK mimicked the disease phenotypes.…”

Bio-electrospraying and aerodynamically assisted bio-jetting the model eukaryotic Dictyostelium discoideum : assessing stress and developmental competency post treatment

“…In these experiments, Dictyostelium is often used as a simple model to analyse human cell movement [ 23 – 25 ]. New roles for Dictyostelium have also been developed as a basic biomedical model [ 26 ], in, for example, the investigation of neuropsychiatric drug targets [ 27 – 30 ], in Alzheimer's disease research [ 31 ], in investigating the mechanisms of microbial infection [ 32 ] and in the analysis of the cellular role of defined proteins identified within the genome [ 33 ].…”