Mitochondria and Cancer: Past, Present, and Future

M L Verschoor,A Harbottle,G Singh,R Ungard,R L Parr,J P Jakupciak

doi:10.1155/2013/612369

M L Verschoor, A Harbottle + Show 4 more

Open Access

https://doi.org/10.1155/2013/612369

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Abstract

The area of mitochondrial genomics has undergone unprecedented growth over the past several years. With the advent of the age of omics, investigations have reached beyond the nucleus to encompass the close biological communication and finely coordinated interactions between mitochondria and their nuclear cell mate. Application of this holistic approach, to all metabolic interactions within the cell, is providing a more complete understanding of the molecular transformation of the cell from normal to malignant behavior, before histopathological indications are evident. In this review the surging momentum in mitochondrial science, as it relates to cancer, is described in three progressive perspectives: (1) Past: the historical contributions to current directions of research; (2) Present: Contemporary findings, results and approaches to mitochondria and cancer, including the role of next generation sequencing and proteomics; (3) Future: Based on the present body of knowledge, the potential assets and benefits of mitochondrial research are projected into the near future.

Highlights

As far back as 1850 scientists identi ed the existence of structures within cells that today we call mitochondria [1]
Mitochondria control various metabolic functions and synthesizes 95% of cellular metabolic energy, while 1,200 nuclear genes drive and participate in mitochondrial function. ere are 37 genes coded for by the mtgenome, 24 of which are dedicated to processing 13 genes within the mtgenome itself which produce the subunits essential to electron transport. ese 13 key genes work in conjunction with 93 nuclear proteins
In cancer cells certain mutations in the mtgenome can alter the biochemical behaviour of mitochondrial/nuclear protein complexes, thereby increasing pools of reactive oxygen species (ROS) which in turn enable tumour growth and may provide proliferative advantage to the cell [11]. us despite its small size relative to the nuclear genome, somatic mutations that occur in the mtgenome are able to contribute directly to the process of tumourigenesis

Summary

Present

Mitochondria play a central role in the regulation of cellular function, metabolism, and cell death in cancer cells. Several important functional changes to cancer cell mitochondrial have been observed that implicate the organelle in tumour formation including increased production of reactive oxygen species (ROS), decreased oxidative phosphorylation, and a corresponding increase in glycolysis [16, 17]. Study of the mechanisms of the Warburg effect has revealed that the characteristic metabolic shi towards aerobic glycolysis and increased glucose uptake imparts several functional advantages to the cancer cell. Excess ROS act as mutagens and initiators of oxidative stress, but are signi cant inter- and intracellular signaling molecules, responsible for a host of nuclear and mitochondrial changes in gene expression, the details of which are reviewed by Verschoor et al [27]. It was recently found that the abundant glutamate excreted as a byproduct of cystine uptake by system xxCC− in cancer cells may initiate several signi cant pathologies of metastatic tumours including excitotoxic cell death in tumours of the CNS, and disruption of bone cell signaling in metastatic tumours in the bone [33, 34]

Genomics of Mitochondrial DNA

A C Normal G T

Findings

Conclusion