Mitochondrial disorders in children: toward development of small-molecule treatment strategies

EMBO Mol Med. 2016 Apr 1;8(4):311-27. doi: 10.15252/emmm.201506131.


This review presents our current understanding of the pathophysiology and potential treatment strategies with respect to mitochondrial disease in children. We focus on pathologies due to mutations in nuclear DNA-encoded structural and assembly factors of the mitochondrial oxidative phosphorylation (OXPHOS) system, with a particular emphasis on isolated mitochondrial complex I deficiency. Following a brief introduction into mitochondrial disease and OXPHOS function, an overview is provided of the diagnostic process in children with mitochondrial disorders. This includes the impact of whole-exome sequencing and relevance of cellular complementation studies. Next, we briefly present how OXPHOS mutations can affect cellular parameters, primarily based on studies in patient-derived fibroblasts, and how this information can be used for the rational design of small-molecule treatment strategies. Finally, we discuss clinical trial design and provide an overview of small molecules that are currently being developed for treatment of mitochondrial disease.

Keywords: children; clinical trial; drug development; mitochondria; outcome measures.

Publication types

  • Review

MeSH terms

  • Child
  • Child, Preschool
  • Clinical Trials as Topic
  • Drug Discovery / trends*
  • Electron Transport Complex I / deficiency
  • Humans
  • Mitochondrial Diseases / diagnosis
  • Mitochondrial Diseases / drug therapy*
  • Mitochondrial Diseases / physiopathology*


  • Electron Transport Complex I