1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine inhibits proton motive force in energized liver mitochondria

Journal Article · Mon May 15 00:00:00 EDT 1989 · Archives of Biochemistry and Biophysics; (USA)

DOI:https://doi.org/10.1016/0003-9861(89)90272-5· OSTI ID:5405252

Singh, Y; Bhatnagar, R; Sidhu, G S; Batra, J K; Krishna, G ^[1]

---

1. National Heart, Lung and Blood Institute, Bethesda, MD (USA)

It is known that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which induces Parkinson's-like disease in primates and humans, depletes hepatocytes of ATP and subsequently causes cell death. Incubation of rat liver mitochondria with MPTP and 1-methyl-4-phenyl pyridinium ion (MPP+) significantly inhibited incorporation of {sup 32}Pi into ATP. MPTP and MPP+ inhibited the development of membrane potential and pH gradient in energized rat liver mitochondria, suggesting that reduction of the proton motive force may have reduced ATP synthesis. Since deprenyl, an inhibitor of monoamine oxidase, prevented the formation of MPP+ and inhibited the decrease in membrane potential caused by MPTP, but not that caused by MPP+, these effects of MPTP, as well as cell death, probably were mediated by MPP+. This mechanism may play a role in the specific loss of dopaminergic neurons resulting in MPTP-induced Parkinson's disease.

• OSTI ID: 5405252
• Journal Information: Archives of Biochemistry and Biophysics; (USA), Vol. 271:1; ISSN 0003-9861
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ATP
BIOSYNTHESIS
NERVOUS SYSTEM DISEASES
PATHOGENESIS
PYRIDINES
BIOCHEMICAL REACTION KINETICS
DOSE-RESPONSE RELATIONSHIPS
ENZYME INHIBITORS
INHIBITION
LIVER CELLS
METABOLISM
MITOCHONDRIA
PHOSPHORUS 32
PROTONS
PYRIDINIUM COMPOUNDS
RATS
TRACER TECHNIQUES
AMINES
AMMONIUM COMPOUNDS
ANIMAL CELLS
ANIMALS
AZINES
BARYONS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CELL CONSTITUENTS
DAYS LIVING RADIOISOTOPES
DISEASES
ELEMENTARY PARTICLES
FERMIONS
HADRONS
HETEROCYCLIC COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGHT NUCLEI
MAMMALS
NUCLEI
NUCLEONS
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
PHOSPHORUS ISOTOPES
QUATERNARY COMPOUNDS
RADIOISOTOPES
REACTION KINETICS
RODENTS
SOMATIC CELLS
SYNTHESIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques
550901 - Pathology- Tracer Techniques