Mitochondria in cancer

The rediscovery and reinterpretation of the Warburg effect in the year 2000 occulted for almost a decade the key functions exerted by mitochondria in cancer cells. Until recent times, the scientific community indeed focused on constitutive glycolysis as a hallmark of cancer cells, which it is not, largely ignoring the contribution of mitochondria to the malignancy of oxidative and glycolytic cancer cells, being Warburgian or merely adapted to hypoxia. In this review, we highlight that mitochondria are not only powerhouses in some cancer cells, but also dynamic regulators of life, death, proliferation, motion and stemness in other types of cancer cells. Similar to the cells that host them, mitochondria are capable to adapt to tumoral conditions, and probably to evolve to ‘oncogenic mitochondria’ capable of transferring malignant capacities to recipient cells. In the wider quest of metabolic modulators of cancer, treatments have already been identified targeting mitochondria in cancer cells, but the field is still in infancy.

Mitochondrial stress management: a dynamic journey

Mitochondria undergo continuous challenges in the course of their life, from their generation to their degradation. These challenges include the management of reactive oxygen species, the proper assembly of mitochondrial respiratory complexes and the need to balance potential mutations in the mitochondrial DNA. The detection of damage and the ability to keep it under control is critical to fine-tune mitochondrial function to the organismal energy needs. In this review, we will analyze the multiple mechanisms that safeguard mitochondrial function in light of in crescendo damage. This sequence of events will include initial defense against excessive reactive oxygen species production, compensation mechanisms by the unfolded protein response (UPRmt), mitochondrial dynamics and elimination by mitophagy.