Role of mitochondria in the etiology and pathogenesis of Parkinson's disease

Biochim Biophys Acta. 1995 May 24;1271(1):265-74. doi: 10.1016/0925-4439(95)00038-6.


We discuss the etiology and pathogenesis of Parkinson's disease (PD). Our group and others have found a decrease in complex I of the mitochondrial electron transfer complex in the substantia nigra of patients with PD; in addition, we reported loss of the alpha-ketoglutarate dehydrogenase complex (KGDHC) in the substantia nigra. Dual loss of complex I and the KGDHC will deleteriously affect the electron transport and ATP synthesis; we believe that energy crisis is the most important mechanism of nigral cell death in PD. Oxidative stress has also been implicated as an important contributor to nigral cell death in PD, but we believe that oxidative stress is a secondary phenomenon to respiratory failure, because respiratory failure will increase oxygen free-radical formation and consume glutathione. The primary cause of mitochondrial respiratory failure has not been elucidated yet, but additive effect of environmental neurotoxins in genetically predisposed persons appears to be the most likely possibility.

Publication types

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

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Brain / metabolism
  • Citric Acid Cycle
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism*
  • Electron Transport
  • Free Radicals / metabolism
  • Glutathione / metabolism
  • Humans
  • Ketoglutarate Dehydrogenase Complex / metabolism
  • Mitochondria / metabolism*
  • Models, Biological
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • Neurotoxins / toxicity
  • Organ Specificity
  • Oxidative Stress
  • Oxygen Consumption
  • Parkinson Disease / etiology
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism*
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / metabolism
  • Polymerase Chain Reaction
  • Reference Values
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology


  • DNA, Mitochondrial
  • Free Radicals
  • Neurotoxins
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Ketoglutarate Dehydrogenase Complex
  • NAD(P)H Dehydrogenase (Quinone)
  • Glutathione