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@ARTICLE{Chenna:283144,
      author       = {Chenna, Sandeep and Joselin, Alvin and Theurey, Pierre and
                      Bano, Daniele and Pizzo, Paola and Ankarcrona, Maria and
                      Park, David S and Prehn, Jochen H and Connolly, Niamh M C},
      title        = {{I}ntegrating simulated and experimental data to identify
                      mitochondrial bioenergetic defects in {P}arkinson's
                      {D}isease models.},
      journal      = {PLOS ONE},
      volume       = {21},
      number       = {1},
      issn         = {1932-6203},
      address      = {San Francisco, California, US},
      publisher    = {PLOS},
      reportid     = {DZNE-2026-00040},
      pages        = {e0339326},
      year         = {2026},
      abstract     = {Mitochondrial 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.},
      keywords     = {Animals / Mitochondria: metabolism / Mitochondria:
                      pathology / Parkinson Disease: metabolism / Parkinson
                      Disease: pathology / Parkinson Disease: genetics / Energy
                      Metabolism / Mice / Disease Models, Animal / Neurons:
                      metabolism / Neurons: pathology / Mice, Knockout / Computer
                      Simulation / Oxygen Consumption / Ubiquitin-Protein Ligases:
                      genetics / Ubiquitin-Protein Ligases: metabolism / Protein
                      Kinases: genetics / Protein Kinases: metabolism / Adenosine
                      Triphosphate: metabolism / Adenosine Triphosphate:
                      biosynthesis / Humans / PTEN-induced putative kinase (NLM
                      Chemicals) / Ubiquitin-Protein Ligases (NLM Chemicals) /
                      Protein Kinases (NLM Chemicals) / Adenosine Triphosphate
                      (NLM Chemicals) / parkin protein (NLM Chemicals)},
      cin          = {AG Bano},
      ddc          = {610},
      cid          = {I:(DE-2719)1013003},
      pnm          = {351 - Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41490258},
      doi          = {10.1371/journal.pone.0339326},
      url          = {https://pub.dzne.de/record/283144},
}