Mitochondrial DNA and primary mitochondrial dysfunction in Parkinson's disease

Mov Disord. 2017 Mar;32(3):346-363. doi: 10.1002/mds.26966. Epub 2017 Mar 2.


In 1979, it was observed that parkinsonism could be induced by a toxin inhibiting mitochondrial respiratory complex I. This initiated the long-standing hypothesis that mitochondrial dysfunction may play a key role in the pathogenesis of Parkinson's disease (PD). This hypothesis evolved, with accumulating evidence pointing to complex I dysfunction, which could be caused by environmental or genetic factors. Attention was focused on the mitochondrial DNA, considering the occurrence of mutations, polymorphic haplogroup-specific variants, and defective mitochondrial DNA maintenance with the accumulation of multiple deletions and a reduction of copy number. Genetically determined diseases of mitochondrial DNA maintenance frequently manifest with parkinsonism, but the age-related accumulation of somatic mitochondrial DNA errors also represents a major driving mechanism for PD. Recently, the discovery of the genetic cause of rare inherited forms of PD highlighted an extremely complex homeostatic control over mitochondria, involving their dynamic fission/fusion cycle, the balancing of mitobiogenesis and mitophagy, and consequently the quality control surveillance that corrects faulty mitochondrial DNA maintenance. Many genes came into play, including the PINK1/parkin axis, but also OPA1, as pieces of the same puzzle, together with mitochondrial DNA damage, complex I deficiency and increased oxidative stress. The search for answers will drive future research to reach the understanding necessary to provide therapeutic options directed not only at limiting the clinical evolution of symptoms but also finally addressing the pathogenic mechanisms of neurodegeneration in PD. © 2017 International Parkinson and Movement Disorder Society.

Keywords: Parkinson disease; mitochondrial DNA; mitophagy; mtDNA; parkinsonism; quality control.

Publication types

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

MeSH terms

  • DNA, Mitochondrial / genetics*
  • Humans
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / metabolism*
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism*


  • DNA, Mitochondrial