title: Tetraphenylborate potentiates the respiratory inhibition by the dopaminergic neurotoxin MPP+ in both electron transport particles and intact mitochondria.
abstract: The cytotoxicity of 1-methyl-4-phenylpyridinium (MPP+) is believed to arise as a consequence of its time- and energy-dependent accumulation inside mitochondria, followed by inhibition of electron transport at Complex I of the respiratory chain. Consistent with our proposal that the accumulation of MPP+ represents a passive Nernstian transport into mitochondria in response to the transmembrane electrochemical potential gradient, tetraphenylborate (TPB-) was found to accelerate the onset of the respiratory inhibition by MPP+ on intact mitochondria. Moreover, the ultimate level of inhibition reached was unexpectedly also increased. The latter is now explained by our finding that TPB- elicits a 12-fold enhancement of MPP+ inhibition of respiration in electron transport particles. It is suggested that TPB- facilitates access of MPP+ to its intramembrane site of inhibitory action in Complex I.
authors: Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106.
authors: L M
authors: LM
authors: Sayre
authors: F
authors: F
authors: Wang
authors: C L
authors: CL
authors: Hoppel
mesh_terms: D015655:1-Methyl-4-phenylpyridinium; D000818:Animals; D001896:Boron Compounds / Q000633:toxicity*; D004357:Drug Synergism; D004579:Electron Transport / Q000187:drug effects*; D066298:In Vitro Techniques; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000648:ultrastructure; D010101:Oxygen Consumption / Q000187:drug effects; D011726:Pyridinium Compounds / Q000633:toxicity*; D051381:Rats; D012995:Solubility; D013367:Submitochondrial Particles / Q000187:drug effects; D013775:Tetraphenylborate / Q000633:toxicity*
chemical_list: D001896:Boron Compounds; D011726:Pyridinium Compounds; D013775:Tetraphenylborate; D015655:1-Methyl-4-phenylpyridinium