Mitochondria in cancer: clean windmills or stressed tinkerers?

• Published in: Trends in cell biology 2023-04, Vol.33 (4), p.293-299
• Main Author: Altieri, Dario C.
• Format: Article
• Language: English
• Subjects: Humans; metabolism; metastasis; Mic60; mitochondria; Mitochondria - metabolism; Neoplasms - pathology; Organelles - metabolism; tumor plasticity
• ISSN: 0962-8924; 1879-3088
• DOI: 10.1016/j.tcb.2022.08.001

There is now a consensus that mitochondria are important tumor drivers, sophisticated biological machines that can engender a panoply of key disease traits. How this happens, however, is still mostly elusive. The opinion presented here is that what cancer exploits are not the normal mitochondria of oxygenated and nutrient-replete tissues, but the unfit, damaged, and dysfunctional organelles generated by the hostile environment of tumor growth. These ‘ghost’ mitochondria survive quality control and thwart cell death to relay multiple comprehensive ‘danger signals’ of metabolic starvation, cellular stress, and reprogrammed gene expression. The result is a new, treacherous cellular phenotype, proliferatively quiescent but highly motile, that enables tumor cell escape from a threatening environment and colonization of distant, more favorable sites (metastasis). Mitochondria are signaling organelles that impact virtually every cellular function.There is now great interest in understanding how mitochondrial functions are exploited in cancer, especially in promoting tumor plasticity and advanced disease traits such as metastasis.The microenvironment of tumor growth is highly unfavorable to mitochondria, as erratic oxygen concentrations, low nutrients, and high oxidative radicals compromise organelle fitness.Loss of mitochondrial fitness is common in cancer, creating highly defective ‘ghost’ mitochondria that relay ‘danger signals’ of metabolic starvation, oxidative stress, and inflammatory and senescence gene expression.