Differential Inhibition/Inactivation of Mitochondrial Complex I Implicates Its Alteration in Malignant Cells

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A. Ghosh¹, S. Bera¹, S. Ghosal¹, S. Ray², A. Basu³, and M. Ray^1*

¹Department of Biological Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India; fax: +91-33-2473-2805; E-mail: bcmr@iacs.res.in

²13 Regent Estate, Kolkata 700092, India

³Department of Surgery, S.S.K.M. Hospital, Kolkata 700020, India

^* To whom correspondence should be addressed.

Received December 14, 2010; Revision received February 22, 2011

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Methylglyoxal strongly inhibited mitochondrial respiration of a wide variety of malignant tissues including sarcoma of mice, whereas no such significant effect was noted on mitochondrial respiration of normal tissues with the exception of cardiac cells. This inhibition by methylglyoxal was found to be at the level of mitochondrial complex I (NADH dehydrogenase) of the electron transport chain. L-Lactaldehyde, which is structurally and metabolically related to methylglyoxal, could protect against this inhibition. NADH dehydrogenase of submitochondrial particles of malignant and cardiac cells was inhibited by methylglyoxal. This enzyme of these cells was also inactivated by methylglyoxal. The possible involvement of lysine residue(s) for the activity of NADH dehydrogenase was also investigated by using lysine-specific reagents trinitrobenzenesulfonic acid (TNBS) and pyridoxal 5′ phosphate (PP). Inactivation of NADH dehydrogenase by both TNBS and PP convincingly demonstrated the involvement of lysine residue(s) for the activity of the sarcoma and cardiac enzymes, whereas both TNBS and PP failed to inactivate the enzymes of skeletal muscle and liver. Together these studies demonstrate a specific effect of methylglyoxal on mitochondrial complex I of malignant cells and importantly some distinct alteration of this complex in cancer cells.

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KEY WORDS: sarcoma, NADH dehydrogenase, methylglyoxal, lactaldehyde

DOI: 10.1134/S0006297911090100

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