Abstract
Mitochondria have traditionally been viewed as the powerhouse of the cell, where they serve, amongst other functions, as a major source of ATP generation. More recently, mitochondria have also been shown to have active roles in a variety of other processes, including apoptotic cell death and inflammation. Here we review the various ways in which mitochondrial functions affect cancer. Although there are many diverse types of cancer, hallmarks have been defined that are applicable to most cancer types. We provide an overview of how mitochondrial functions affect some of these hallmarks, which include evasion of cell death, de-regulated bioenergetics, genome instability, tumour-promoting inflammation and metastasis. In addition to discussing the underlying mitochondrial roles in each of these processes, we also highlight the considerable potential of targeting mitochondrial functions to improve cancer treatment.
Highlights
Cancer is a highly diverse disease that is comprised of over two hundred different types
In addition to the Warburg effect, as we will discuss more specific alterations in metabolic pathways have been identified in certain cancers, many of which track back to loss or gain of function mutations in key enzymes involved in mitochondrial metabolism
Tfam heterozygosity promotes tumourigenesis in a mouse model of colorectal cancer in a manner that can be inhibited by transgenic expression of the anti-oxidant enzyme, mitochondrial-targeted catalase [34]
Summary
Cancer is a highly diverse disease that is comprised of over two hundred different types. In addition to the Warburg effect, as we will discuss more specific alterations in metabolic pathways have been identified in certain cancers, many of which track back to loss or gain of function mutations in key enzymes involved in mitochondrial metabolism. Both oncogenic and tumour suppressor pathways have been shown to directly effect a variety of mitochondrial metabolic pathways, strongly supporting the notion that deregulated metabolism underpins cancer development and progression.
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