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000283144 1001_ $$00000-0003-2297-7691$$aChenna, Sandeep$$b0
000283144 245__ $$aIntegrating simulated and experimental data to identify mitochondrial bioenergetic defects in Parkinson's Disease models.
000283144 260__ $$aSan Francisco, California, US$$bPLOS$$c2026
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000283144 520__ $$aMitochondrial bioenergetics are vital for ATP production and are associated with several diseases, including Parkinson's Disease (PD). Here, we simulated a computational model of mitochondrial ATP production to interrogate mitochondrial bioenergetics under physiological and pathophysiological conditions, and provide a data resource that can be used to interpret mitochondrial bioenergetics experiments. We first characterised the impact of several common electron transport chain (ETC) impairments on experimentally-observable bioenergetic parameters. We then established an analysis pipeline to integrate simulations with experimental data and predict the molecular defects underlying experimental bioenergetic phenotypes. We applied the pipeline to data from PD models. We verified that the impaired bioenergetic profile previously measured in Parkin knockout (KO) neurons can be explained by increased mitochondrial uncoupling. We then generated primary cortical neurons from a Pink1 KO mouse model of PD, and measured reduced oxygen consumption rate (OCR) capacity and increased resistance to Complex III inhibition. Here, our pipeline predicted that multiple impairments are required to explain this bioenergetic phenotype. Finally, we provide all simulated data as a user-friendly resource that can be used to interpret mitochondrial bioenergetics experiments, predict underlying molecular defects, and inform experimental design.
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000283144 650_7 $$0EC 2.7.11.1$$2NLM Chemicals$$aPTEN-induced putative kinase
000283144 650_7 $$0EC 2.3.2.27$$2NLM Chemicals$$aUbiquitin-Protein Ligases
000283144 650_7 $$0EC 2.7.-$$2NLM Chemicals$$aProtein Kinases
000283144 650_7 $$08L70Q75FXE$$2NLM Chemicals$$aAdenosine Triphosphate
000283144 650_7 $$0EC 2.3.2.27$$2NLM Chemicals$$aparkin protein
000283144 650_2 $$2MeSH$$aAnimals
000283144 650_2 $$2MeSH$$aMitochondria: metabolism
000283144 650_2 $$2MeSH$$aMitochondria: pathology
000283144 650_2 $$2MeSH$$aParkinson Disease: metabolism
000283144 650_2 $$2MeSH$$aParkinson Disease: pathology
000283144 650_2 $$2MeSH$$aParkinson Disease: genetics
000283144 650_2 $$2MeSH$$aEnergy Metabolism
000283144 650_2 $$2MeSH$$aMice
000283144 650_2 $$2MeSH$$aDisease Models, Animal
000283144 650_2 $$2MeSH$$aNeurons: metabolism
000283144 650_2 $$2MeSH$$aNeurons: pathology
000283144 650_2 $$2MeSH$$aMice, Knockout
000283144 650_2 $$2MeSH$$aComputer Simulation
000283144 650_2 $$2MeSH$$aOxygen Consumption
000283144 650_2 $$2MeSH$$aUbiquitin-Protein Ligases: genetics
000283144 650_2 $$2MeSH$$aUbiquitin-Protein Ligases: metabolism
000283144 650_2 $$2MeSH$$aProtein Kinases: genetics
000283144 650_2 $$2MeSH$$aProtein Kinases: metabolism
000283144 650_2 $$2MeSH$$aAdenosine Triphosphate: metabolism
000283144 650_2 $$2MeSH$$aAdenosine Triphosphate: biosynthesis
000283144 650_2 $$2MeSH$$aHumans
000283144 7001_ $$00000-0002-9010-0421$$aJoselin, Alvin$$b1
000283144 7001_ $$aTheurey, Pierre$$b2
000283144 7001_ $$0P:(DE-2719)2158358$$aBano, Daniele$$b3$$udzne
000283144 7001_ $$aPizzo, Paola$$b4
000283144 7001_ $$aAnkarcrona, Maria$$b5
000283144 7001_ $$aPark, David S$$b6
000283144 7001_ $$00000-0003-3479-7794$$aPrehn, Jochen H$$b7
000283144 7001_ $$00000-0002-6005-1307$$aConnolly, Niamh M C$$b8
000283144 773__ $$0PERI:(DE-600)2267670-3$$a10.1371/journal.pone.0339326$$gVol. 21, no. 1, p. e0339326 -$$n1$$pe0339326$$tPLOS ONE$$v21$$x1932-6203$$y2026
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