INFORMAZIONI SU

GISSI Clarissa

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Supervisori: Prof. Grassi e Dott.ssa Comelli

Neuromuscular ageing: Mechanisms and functional implications (NeuAge)

Poster scientifico

My PhD project mainly focused on mitochondrial alterations in two different skeletal muscle-associated diseases: sarcopenia and a specific spastic paraplegia/dystonia. The aim of the first project is to use 18-month-old Pin1 KO mice, a model characterised by a delay in sarcopenia. Mitochondrial respiration and ADP sensitivity were evaluated, using high-resolution respirometry, on permeabilized tibialis anterior skeletal muscle fibres obtained by biopsies. The data were normalized with respect to citrate synthase activity. Moreover, the proteins involved in the molecular mechanisms that modify the availability of ADP across the external and internal mitochondrial membranes were also investigated by Western blotting. The second project focused on a novel ATP5MC3 gene variant, that leads to N106K substitution in the c3 subunit of mitochondrial ATP synthase and those results associated with a spastic paraplegia and/or dystonia. Through in vitro experiments on skin fibroblast obtained from a patient and control, the impact of this mutation on the mitochondrial respiration and on the content of the OXPHOS complexes, CyPD and other subunits of ATP synthase involved in permeability transition pore formation (PTP) were evaluated. The propensity of these fibroblasts to undergo opening of the PTP, by a calcein fluorescence assay in confocal microscopy time-laps analyses was also evaluated. These studies will help to elucidate molecular mechanisms involved in this rare pathology and could be crucial to find new therapies.