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Differential inhibition/inactivation of mitochondrial complex I implicates its alteration in malignant cells

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Abstract

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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Abbreviations

DTNB:

5,5′-dithiobis(2-nitrobenzoic acid)

DTT:

dithiothreitol

EAC:

Ehrlich ascites carcinoma

MG:

methylglyoxal

α-OG:

α-oxoglutarate

PP:

pyridoxal 5′ phosphate

SMP:

submitochondrial particles

TMPD:

N,N,N′,N′-tetramethyl-p-phenylenediamine

TNBS:

trinitrobenzenesulfonic acid

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Authors and Affiliations

  1. Department of Biological Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, 700032, India

    A. Ghosh, S. Bera, S. Ghosal & M. Ray

  2. 13 Regent Estate, Kolkata, 700092, India

    S. Ray

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

    A. Basu

Authors
  1. A. Ghosh
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  2. S. Bera
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  3. S. Ghosal
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  4. S. Ray
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  5. A. Basu
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  6. M. Ray
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Corresponding author

Correspondence to M. Ray.

Additional information

Published in Russian in Biokhimiya, 2011, Vol. 76, No. 9, pp. 1289–1299.

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Ghosh, A., Bera, S., Ghosal, S. et al. Differential inhibition/inactivation of mitochondrial complex I implicates its alteration in malignant cells. Biochemistry Moscow 76, 1051–1060 (2011). https://doi.org/10.1134/S0006297911090100

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  • DOI: https://doi.org/10.1134/S0006297911090100

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