Is there a role for mitochondrial genes in carcinogenesis?

Although defective respriration is not characteristic of all tumors, recent comparative studies on the ultrastructure of normal and tumor cell mitochondria indicate that in malignant cells mitochondria deviate from normal not only in relative abundance but also in the size, form, density, and frequency of appearance of lesions. Normal and abnormal mitochondria may populate the same cell, suggesting that there may be a gradation in respiratory deficiency depending on the proportion of normal to abnormal forms. Recent advances in mitochondrial genetics suggest that aberrant mitochondria may be formed as a result of the presence of an abnormal mitochondrial genome. In analogy with the petite mutant of certain strains of yeast, animal cells may be transformed by treatment with dyes that alter the structure of their mitochondrial DNA, so that their mitochondria also become deficient in enzymes of the respiratory chain. Whether nutritional or other deficiencies are mutagenic with respect to mitochondrial DNA of animal cells is not known; nor is it known whether mitochondrial mutagenesis is causally involved in carcinogenesis. New knowledge of cytoplasmic genetics and of mitochondrial DNA and membrane structure and dynamics should encourage investigations aimed at examining the possible role of mitochondrial genes in neoplastic transformation.