Inhibition of complex I by Ca2+ reduces electron transport activity and the rate of superoxide anion production in cardiac submitochondrial particles.

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Matsuzaki S, Szweda LI

Inhibition of complex I by Ca2+ reduces electron transport activity and the rate of superoxide anion production in cardiac submitochondrial particles.

Biochemistry. 2007 Feb 6;46(5):1350-7.

PubMed ID

17260964 [ View in PubMed

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Abstract

Declines in the rate of mitochondrial electron transport and subsequent increases in the half-life of reduced components of the electron transport chain can stimulate O2*- formation. We have previously shown that, in solubilized cardiac mitochondria, Ca2+ mediates reversible free radical-induced inhibition of complex I. In the study presented here, submitochondrial particles prepared from rat heart were utilized to determine the effects of Ca2+ on specific components of the respiratory chain and on the rates of electron transport and O2*- production. The results indicate that complex I is inactivated when submitochondrial particles are treated with Ca2+. Inactivation was specific to complex I with no alterations in the activities of other electron transport chain complexes. Complex I inactivation by Ca2+ resulted in the reduction of NADH-supported electron transport activity. In contrast to the majority of electron transport chain inhibitors, Ca2+ suppressed the rate of O2*- production. In addition, while inhibition of complex III stimulated O2*- production, Ca2+ reduced the relative rate of O2*- production, consistent with the magnitude of complex I inhibition. Evidence indicates that complex I is the primary source of O2*- released from this preparation of submitochondrial particles. Ca2+ therefore inhibits electron transport upstream of site(s) of free radical production. This may represent a means of limiting O2*- production by a compromised electron transport chain.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
NADH	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial	Protein	Humans	Unknown	Not Available	Details