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The striking differences in the bioenergetics of brain and liver mitochondria are enhanced in mitochondrial disease.
Balmaceda, Valeria; Komlódi, Timea; Szibor, Marten; Gnaiger, Erich; Moore, Anthony L; Fernandez-Vizarra, Erika; Viscomi, Carlo.
Afiliación
  • Balmaceda V; Department of Biomedical Sciences, University of Padova, Padova, Italy.
  • Komlódi T; Department of Biochemistry and Molecular Biology, Semmelweis University, Budapest, Hungary; Oroboros Instruments, Schöpfstr. 18, 6020 Innsbruck, Austria.
  • Szibor M; Department of Cardiothoracic Surgery, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Friedrich Schiller University of Jena, Jena, Germany; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
  • Gnaiger E; Oroboros Instruments, Schöpfstr. 18, 6020 Innsbruck, Austria.
  • Moore AL; Biochemistry & Biomedicine, School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK. Electronic address: a.l.moore@sussex.ac.uk.
  • Fernandez-Vizarra E; Department of Biomedical Sciences, University of Padova, Padova, Italy; Veneto Institute of Molecular Medicine, Padova, Italy. Electronic address: erika.fernandezvizarra@unipd.it.
  • Viscomi C; Department of Biomedical Sciences, University of Padova, Padova, Italy; Veneto Institute of Molecular Medicine, Padova, Italy. Electronic address: carlo.viscomi@unipd.it.
Biochim Biophys Acta Mol Basis Dis ; 1870(3): 167033, 2024 03.
Article en En | MEDLINE | ID: mdl-38280294
ABSTRACT
Mitochondrial disorders are hallmarked by the dysfunction of oxidative phosphorylation (OXPHOS) yet are highly heterogeneous at the clinical and genetic levels. Striking tissue-specific pathological manifestations are a poorly understood feature of these conditions, even if the disease-causing genes are ubiquitously expressed. To investigate the functional basis of this phenomenon, we analyzed several OXPHOS-related bioenergetic parameters, including oxygen consumption rates, electron transfer system (ETS)-related coenzyme Q (mtCoQ) redox state and production of reactive oxygen species (ROS) in mouse brain and liver mitochondria fueled by different substrates. In addition, we determined how these functional parameters are affected by ETS impairment in a tissue-specific manner using pathologically relevant mouse models lacking either Ndufs4 or Ttc19, leading to Complex I (CI) or Complex III (CIII) deficiency, respectively. Detailed OXPHOS analysis revealed striking differences between brain and liver mitochondria in the capacity of the different metabolic substrates to fuel the ETS, reduce the ETS-related mtCoQ, and to induce ROS production. In addition, ETS deficiency due to either CI or CIII dysfunction had a much greater impact on the intrinsic bioenergetic parameters of brain compared with liver mitochondria. These findings are discussed in terms of the still rather mysterious tissue-specific manifestations of mitochondrial disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mitocondrias Hepáticas / Enfermedades Mitocondriales Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mitocondrias Hepáticas / Enfermedades Mitocondriales Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Países Bajos