The Role of Mitochondria in Carcinogenesis

Abstract

The mitochondria are essential for normal cell functioning. Changes in mitochondrial DNA (mtDNA) may affect the occurrence of some chronic diseases and cancer. This process is complex and not entirely understood. The assignment to a particular mitochondrial haplogroup may be a factor that either contributes to cancer development or reduces its likelihood. Mutations in mtDNA occurring via an increase in reactive oxygen species may favour the occurrence of further changes both in mitochondrial and nuclear DNA. Mitochondrial DNA mutations in postmitotic cells are not inherited, but may play a role both in initiation and progression of cancer. One of the first discovered polymorphisms associated with cancer was in the gene NADH-ubiquinone oxidoreductase chain 3 (mt-ND3) and it was typical of haplogroup N. In prostate cancer, these mutations and polymorphisms involve a gene encoding subunit I of respiratory complex IV cytochrome c oxidase subunit 1 gene (COI). At present, a growing number of studies also address the impact of mtDNA polymorphisms on prognosis in cancer patients. Some of the mitochondrial DNA polymorphisms occur in both chronic disease and cancer, for instance polymorphism G5913A characteristic of prostate cancer and hypertension.

Keywords: cancer; mtDNA; mutagenesis; polymorphism.

Figure 1

Glycolytic ATP contribution in tumour and normal cells expressed as a percentage of total ATP production (based on Zu and Guppy [38]).

Figure 2

Glycolytic ATP contribution in tumour and normal cells–Oxidative ATP production (based on Zu and Guppy [38]).

Figure 3

Reverse Warburg effect. Reactive Oxygen Species (ROS) secreted by cancer cells induce aerobic glycolysis in neighboring stromal fibroblasts. The high-energy compounds produced as a result of aerobic glycolysis are transported back to the cancer cells. These compounds are to be used for anabolic processes and the formation of ATP in the process of aerobic respiration by cancer cells, which is assumed to contribute to the progression of cancer. MCTs-monocarboxylate transporters,-plasma membrane transporters that carry molecules having one carboxylate group.