Mitochondrial Dysfunction in Cancer

Abstract

A mechanistic understanding of how mitochondrial dysfunction contributes to cell growth and tumorigenesis is emerging beyond Warburg as an area of research that is under-explored in terms of its significance for clinical management of cancer. Work discussed in this review focuses less on the Warburg effect and more on mitochondria and how dysfunctional mitochondria modulate cell cycle, gene expression, metabolism, cell viability, and other established aspects of cell growth and stress responses. There is increasing evidence that key oncogenes and tumor suppressors modulate mitochondrial dynamics through important signaling pathways and that mitochondrial mass and function vary between tumors and individuals but the significance of these events for cancer are not fully appreciated. We explore the interplay between key molecules involved in mitochondrial fission and fusion and in apoptosis, as well as in mitophagy, biogenesis, and spatial dynamics of mitochondria and consider how these distinct mechanisms are coordinated in response to physiological stresses such as hypoxia and nutrient deprivation. Importantly, we examine how deregulation of these processes in cancer has knock on effects for cell proliferation and growth. We define major forms of mitochondrial dysfunction and address the extent to which the functional consequences of such dysfunction can be determined and exploited for cancer diagnosis and treatment.

Editorial Mitochondria, brain, heart and body

“…It has been repeatedly reported to be found in heart diseases, neurological disorders and cancers [6,10,11,12].…”

Darwinian Principles in Cancer Therapy

“…15 For example, mitochondrial dysfunction in tumour cells may have no evolutionary advantage in the absence of a potent selective force and lead to growth retardation due to reduced cell cycle progression. 25 This sub-clone is unlikely to become dominant within a tumour. However, upon the introduction of a selective force, such as chemotherapy acting on the mitochondrial apoptosis pathway, 4 the same mitochondrial deficiency might confer increased resistance to cell death, 25 thus exerting a positive selective pressure, causing dominance of this particular sub-clone and thus the growth of a therapy-resistant tumour.…”

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives

“…Maintenance of mitochondrial function involves interaction of multiple complex pathways [156, 165], which can be inhibited by AEDs to compromise normal mitochondrial function [156]. The mechanisms behind AED-mediated mitochondrial dysfunction in the case of drugs such as carbamazepine, phenytoin and valproic acid are generally well studied [156] and will be detailed below.…”