Uncoupling of mitochondrial oxidative phosphorylation by DNA gyrase inhibitors
Supercoiled mtDNA and the swivel requirement for its replication suggest the existence of a mtDNA gyrase. The authors published studies on isolated mitochondria showing that novobiocin, coumermycin, nalidixic acid, and oxolinic acid promote relaxed DNA formation at the expense of supercoiled DNA are in accord with this view. However, their inability to directly detect the enzyme led them to ask whether these drugs act elsewhere. Their results with isolated rat liver mitochondria show that novo, nal, but not oxo, stimulate O/sub 2/ uptake as much as does 2.4-dinitrophenol (DNP). This possible uncoupling effect was confirmed by a standard (/sup 32/P) assay showing the following inhibitions of ATP synthesis: 0.2 mM novo, 95% (0.4 mM, 100%) 0.4 mM nal, 37%; oxo to at least 1.9 mM, 0%; (0.5 mM 2,4-DNP, 100%). Thus, oxo remains a useful tool for intact mitochondrial studies. Because these three drugs, especially novo, are being used to study the role of DNA superhelicity on pro- and eucaryotic (and mitochondrial) gene expression, the authors studied their effect on oxidative phosphorylation in such cells. In these cases the drugs did not affect DNP-sensitive (/sup 14/C)glutamine transport into E. coli cells (an established measure of ATP level), nor, in an S. cerevisiae mutant permeable to novo, did novo affect the steady state ATP level. Studies on cultured mammalian cells are in progress.
- Research Organization:
- State Univ. of New York, Stony Brook
- OSTI ID:
- 5117485
- Report Number(s):
- CONF-8606151-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:6; ISSN FEPRA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMIDES
AMINO ACIDS
ANIMALS
AROMATICS
ATP
BACTERIA
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CHEMICAL REACTIONS
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DNA
DNA REPLICATION
ENZYME INHIBITORS
ESCHERICHIA COLI
FUNGI
GLANDS
GLUTAMINE
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
LIVER
MAMMALS
MICROORGANISMS
MITOCHONDRIA
NITRO COMPOUNDS
NITROPHENOL
NUCLEI
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
ORGANS
PHENOLS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORYLATION
PLANTS
RADIOISOTOPES
RATS
RODENTS
SACCHAROMYCES
SACCHAROMYCES CEREVISIAE
TRACER TECHNIQUES
VERTEBRATES
YEASTS