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Vaupel MiP2010

From Bioblast
Vaupel P, Mayer A (2010) Evidence against a mitochondrial dysfunction in cancer cells as a hallmark of malignant growth. Abstract MiP2010.

Link: Abstracts Session 4

Vaupel P, Mayer A (2010)

Event: MiP2010

After several decades, the Pasteur-, Crabtree- and Warburg effects have experienced a renaissance in current research. The interaction between glycolysis (i.e., the direct breakdown of glucose to lactate/lactic acid) and mitochondrial oxidative phosphorylation (i.e., glucose oxidation) was first described by Pasteur in 1857.


Labels: MiParea: Respiration  Pathology: Cancer 


Preparation: Intact cells 

Regulation: Aerobic glycolysis, Substrate  Coupling state: OXPHOS 



Full text

After several decades, the Pasteur-, Crabtree- and Warburg-effects have experienced a renaissance in current research. The interaction between glycolysis (i.e., the direct breakdown of glucose to lactate/lactic acid) and mitochondrial oxidative phosphorylation (i.e., glucose oxidation) was first described by Pasteur in 1857. He found a decrease in the rate of glycolysis, and thus a drop in lactate formation in tissues when oxygen was provided to cells metabolizing anaerobically (Pasteur-effect). The Crabtree-effect is the converse of the Pasteur-effect: Inhibition of cellular oxygen consumption on administration of extra glucose to cells having a high rate of glycolysis. In oncology, the Warburg-effect describes the observation that cancer cells (predominantly) convert glucose to lactate even in conditions of adequate oxygen supply (aerobic glycolysis, for reviews see (1,2)). Warburg attributed the latter metabolic alteration to mitochondrial “respiration injury” and considered this as the key metabolic change in malignant transformation (“origin of cancer cells” (3)). Warburg’s interpretation of his data was originally questioned by Weinhouse (4), showing that the production of lactate of the retina, the renal medulla and other normal tissues were as high as that of many tumours. The glycolytic ATP contribution in normal cells was shown to be 20±21% and thus not different from that of tumour cells (17±18%). Reviewing the data from the last five decades, it has been concluded that there is no clear evidence that cancer cells in general are inherently glycolytic, but that some tumours might indeed be glycolytic in vivo merely as a result of hypoxic response mechanisms (5).

Here we present a series of experimental data which clearly exclude mitochondrial dysfunction in cancer cells as a general hallmark of malignancy. These tumour pathophysiology-based data include increasing oxygen uptake rates by cancer cells as a function of:

  • increasing blood flow (i.e., increasing oxygen supply (6));
  • increasing haemoglobin concentration in the blood (i.e., increasing oxygen carrying capacity);
  • increasing oxygen tensions in the arterial blood (90-450 mmHg); and
  • increasing tumour tissue temperatures (4-40°C).

In addition, intact and functional cytochromes detected in many tumour cells clearly speak against a mitochondrial dysfunction (B. Chance, personal communication).

1. van der Heiden MG et al. (2009) Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science 324: 1029-1033.

2. Mayevsky A (2009) Mitochondrial function and energy metabolism in cancer cells: Past overview and future perspectives. Mitochondrion 9: 165-179.

3. Warburg O (1956) On the origin of cancer cells. Science 123: 309-314.

4. Weinhouse S (1956) On respiratory impairment in cancer cells. Science 124: 267-268.

5. Xu XL, Guppy M (2004) Cancer metabolism: Facts, fantasy, and fiction. Biochem. Biophys. Res. Commun. 313: 459-465.

6. Vaupel P (1977) Hypoxia in neoplastic tissue. Microvasc. Res. 13: 399-408.