After winning the 1932 Nobel in Physiology for arguing that cancer is essentially a mitochondrial disease, Dr. Otto H. Warburg‘s theory later became controversial when evidence came to show that genetic mutations are to blame. Now researchers are putting another curve in the road, as new emerging science is showing that Dr. Warburg may not have been wrong at all.
Boston College press office explains:
In contrast to healthy cells, which generate energy by the oxidative breakdown of a simple acid within the mitochondria, tumors and cancer cells generate energy through the non-oxidative breakdown of glucose, a process called glycolysis. Indeed, glycolysis is the biochemical hallmark of most, if not all, types of cancers. Because of this difference between healthy cells and cancer cells, Warburg argued, cancer should be interpreted as a type of mitochondrial disease.
In the years that followed, Warburg’s theory inspired controversy and debate as researchers instead found that genetic mutations within cells caused malignant transformation and uncontrolled cell growth. Many researchers argued Warburg’s findings really identified the effects, and not the causes, of cancer since no mitochondrial defects could be found that were consistently associated with malignant transformation in cancers.
Boston College biologists and colleagues at Washington University School of Medicine found new evidence to support Warburg’s theory by examining mitochondrial lipids in a diverse group of mouse brain tumors, specifically a complex lipid known as cardiolipin (CL). They reported their findings in the December edition of the Journal of Lipid Research.
Abnormalities in cardiolipin can impair mitochondrial function and energy production. Boston College doctoral student Michael Kiebish and Professors Thomas N. Seyfried and Jeffrey Chuang compared the cardiolipin content in normal mouse brain mitochondria with CL content in several types of brain tumors taken from mice. Bioinformatic models were used to compare the lipid characteristics of the normal and the tumor mitochondria samples. Major abnormalities in cardiolipin content or composition were present in all types of tumors and closely associated with significant reductions in energy-generating activities.
The findings were consistent with the pivotal role of cardiolipin in maintaining the structural integrity of a cell’s inner mitochondrial membrane, responsible for energy production. The results suggest that cardiolipin abnormalities “can underlie the irreversible respiratory injury in tumors and link mitochondrial lipid defects to the Warburg theory of cancer,” according to the co-authors.
Press release: Nearly a century later, new findings support Warburg theory of cancer …
Image: These three-dimensional illustrations show the relationship of cardiolipin abnormalities to electron transport chain activities in the cells of mouse brain tumors studied by researchers from Boston College and Washington University School of Medicine. The graphs show the position of the tumors in relation to their host strain in three enzyme complexes. Credit: The Journal of Lipid Research