Nitric oxide as a competitive inhibitor of oxygen consumption in the mitochondrial respiratory chain

Although Escherichia coli LPS is known to elicit various proinflammatory responses in macrophages, its effect on the translational states of transcripts has not yet been explored on a genome-wide scale. To address this, we investigated the mRNA profiles in polysomal and free messenger ribonucleoprotein particle (mRNP) fractions of mouse macrophage-like J774.1 cells, using Affymetrix Mouse Genome 430 2.0 GeneChips. Comparison of the mRNA profiles in total cellular, polysomal, and free mRNP fractions enabled us to identify transcripts that were modulated at the translational level by LPS: among 19,791 transcripts, 115 and 418 were up- and downregulated at 1, 2, or 4 h after LPS stimulation (100 ng/ml) in a translation-dependent manner. Interestingly, gene ontology-based analysis suggested that translation-dependent downregulated genes frequently include those encoding proteins in the mitochondrial respiratory chain. In fact, the mRNA levels of some transcripts for complexes I, IV, and V in the mitochondrial respiratory chain were translationally downregulated, eventually contributing to the decline of their protein levels. Moreover, the amount of metabolically labeled cytochrome oxidase subunit Va in complex IV was decreased without any change of its mRNA level in total cellular fraction after LPS stimulation. Consistently, the total amounts and activities of complexes I and IV were attenuated by LPS stimulation, and the attenuation was independent of nitric oxide. These results demonstrated that translational suppression may play a critical role in the LPS-mediated attenuation of mitochondrial oxidative phosphorylation in a nitric oxide-independent manner in J774.1 cells.

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Impact of diabetes-associated lipoproteins on oxygen consumption, enzymatic activities of mitochondrial respiratory chain complexes

Biochimica et Biophysica Acta (BBA) - Bioenergetics ◽

10.1016/j.bbabio.2010.04.175 ◽

2010 ◽

Vol 1797 ◽

pp. 53-54

Author(s):

Subir Roy Chowdhury ◽

Ganesh Sangle ◽

Xueping Xue ◽

Garry Shen

Keyword(s):

Oxygen Consumption ◽

Respiratory Chain ◽

Mitochondrial Respiratory Chain ◽

Enzymatic Activities ◽

Respiratory Chain Complexes ◽

Chain Complexes ◽

Mitochondrial Respiratory

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Inhibition of electron flow through complex I of the mitochondrial respiratory chain of Ehrlich ascites carcinoma cells by methylglyoxal

Biochemical Journal ◽

10.1042/bj3030069 ◽

1994 ◽

Vol 303 (1) ◽

pp. 69-72 ◽

Cited By ~ 57

Author(s):

S Ray ◽

S Dutta ◽

J Halder ◽

M Ray

Keyword(s):

Oxygen Consumption ◽

Respiratory Chain ◽

Complex I ◽

Electron Flow ◽

Mitochondrial Respiratory Chain ◽

Ehrlich Ascites Carcinoma ◽

Inhibitory Effect ◽

Ehrlich Ascites ◽

Flow Through ◽

Mitochondrial Respiratory

The effect of methylglyoxal on the oxygen consumption of Ehrlich-ascites-carcinoma (EAC)-cell mitochondria was tested by using different respiratory substrates, electron donors at different segments of the mitochondrial respiratory chain and site-specific inhibitors to identify the specific respiratory complex which might be involved in the inhibitory effect of methylglyoxal on the oxygen consumption by these cells. The results indicate that methylglyoxal strongly inhibits ADP-stimulated alpha-oxo-glutarate and malate plus pyruvate-dependent respiration, whereas, at a much higher concentration, methylglyoxal fails to inhibit succinate-dependent respiration. Methylglyoxal also fails to inhibit respiration which is initiated by duroquinol, an artificial electron donor. Moreover, methylglyoxal cannot inhibit oxygen consumption when the NNN'N′-tetramethyl-p-phenylenediamine by-pass is used. The inhibitory effect of methylglyoxal is identical on both ADP-stimulated and uncoupler-stimulated respiration. Lactaldehyde, a catabolite of methylglyoxal, can exert a protective effect on the inhibition of EAC-cell mitochondrial respiration by methylglyoxal. We suggest that methylglyoxal possibly inhibits the electron flow through complex I of the EAC-cell mitochondrial respiratory chain.

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