Isolated mitochondrial complex I deficiency: explorative data analysis of patient cell parameters

Curr Pharm Des. 2011 Dec 1;17(36):4023-33. doi: 10.2174/138161211798764870.


Mitochondrial dysfunction has been implicated in many human diseases and off-target drug effects. Isolated deficiency of mitochondrial complex I (CI), the first complex of the oxidative phosphorylation (OXPHOS) system, can arise from mutations in nuclear DNA (nDNA)-encoded subunits. In humans, these mutations are generally associated with neurodegenerative disorders like Leigh or Leigh-like syndrome with onset in early childhood. Currently, no cure or mitigative treatment is available for these diseases. To aid the future design of rational treatment strategies, insight into the pathophysiology of CI mutations is required. To this end, we quantitatively compared various cell physiological readouts between fibroblasts from healthy individuals and patients with isolated CI deficiency. Here we review how this multivariate dataset was obtained and in which way explorative data analysis (EDA) techniques can be used for pattern analysis. Based upon 13 experimental parameters two patient groups were identified. These displayed a later (cluster I) or earlier (cluster II) age of disease onset and death. Relative to cluster I, cluster II patient cells displayed a larger reduction in CI activity, a larger increase in NADH/ROS levels, mitochondrial fragmentation and lower cellular levels of OXPHOS proteins. Our results highlight a connection between CI deficiency, ROS and mitochondrial morphology/function. This information not only contributes to our understanding of the pathophysiological mechanism of CI and mitochondrial deficiency but also suggests possible targets for cellular intervention strategies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Calcium / metabolism
  • Cluster Analysis
  • Electron Transport
  • Electron Transport Complex I / deficiency
  • Electron Transport Complex I / metabolism
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Humans
  • Lipid Peroxidation
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Mitochondrial Diseases* / metabolism
  • Mitochondrial Diseases* / pathology
  • Oxidation-Reduction
  • Principal Component Analysis
  • Reactive Oxygen Species / metabolism*
  • Sulfhydryl Compounds / metabolism


  • Reactive Oxygen Species
  • Sulfhydryl Compounds
  • Adenosine Triphosphate
  • Electron Transport Complex I
  • Calcium

Supplementary concepts

  • Mitochondrial complex I deficiency