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

Y Mizuno; S Ikebe; N Hattori; Y Nakagawa-Hattori; H Mochizuki; M Tanaka; T Ozawa

doi:10.1016/0925-4439(95)00038-6

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.

Authors

Y Mizuno¹, S Ikebe, N Hattori, Y Nakagawa-Hattori, H Mochizuki, M Tanaka, T Ozawa

Affiliation

¹ Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.

PMID: 7599219
DOI: 10.1016/0925-4439(95)00038-6

Abstract

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

Substances

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