Assembly of mitochondrial complex I and defects in disease

Biochim Biophys Acta. 2009 Jan;1793(1):78-88. doi: 10.1016/j.bbamcr.2008.04.015. Epub 2008 May 4.


Isolated complex I deficiency is the most common cause of respiratory chain dysfunction. Defects in human complex I result in energy generation disorders and they are also implicated in neurodegenerative disease and altered apoptotic signaling. Complex I dysfunction often occurs as a result of its impaired assembly. The assembly process of complex I is poorly understood, complicated by the fact that in mammals, it is composed of 45 different subunits and is regulated by both nuclear and mitochondrial genomes. However, in recent years we have gained new insights into complex I biogenesis and a number of assembly factors involved in this process have also been identified. In most cases, these factors have been discovered through their gene mutations that lead to specific complex I defects and result in mitochondrial disease. Here we review how complex I is assembled and the factors required to mediate this process.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis Inducing Factor / metabolism
  • Cell Nucleus / metabolism
  • DNA / metabolism
  • Electron Transport Complex I / chemistry
  • Electron Transport Complex I / metabolism*
  • Humans
  • Mitochondria / metabolism*
  • Mitochondrial Diseases / metabolism*
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / metabolism*
  • Models, Biological
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism


  • Apoptosis Inducing Factor
  • Mitochondrial Proteins
  • Protein Subunits
  • DNA
  • Electron Transport Complex I