The striking differences in the bioenergetics of brain and liver mitochondria are enhanced in mitochondrial disease

Valeria Balmaceda, Timea Komlódi, Marten Szibor, Erich Gnaiger, Anthony L. Moore, Erika Fernandez-Vizarra, Carlo Viscomi

Research output: Contribution to journalArticleScientificpeer-review


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.

Original languageEnglish
Article number167033
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number3
Publication statusPublished - Mar 2024
Publication typeA1 Journal article-refereed


  • Coenzyme Q redox state
  • Complex I deficiency
  • Complex III deficiency
  • Isolated mitochondria
  • Oxygen consumption
  • Reactive oxygen species

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology


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