Mitochondrial bioenergetics of breast cancer.

ABSTRACT

Breast cancer cells exhibit metabolic heterogeneity based on tumour aggressiveness. Glycolysis and mitochondrial respiration are two major metabolic pathways for ATP production. The oxygen flux, oxygen tension, proton leakage, protonmotive force, inner mitochondrial membrane potential, ECAR and electrochemical proton gradient maintain metabolic homeostasis, ATP production, ROS generation, heat dissipation, and carbon flow and are referred to as "sub-domains" of mitochondrial bioenergetics. Tumour aggressiveness is influenced by these mechanisms, especially when breast cancer cells undergo metastasis. These physiological parameters for healthy mitochondria are as crucial as energy demands for tumour growth and metastasis. The instant energy demands are already elucidated under Warburg effects, while these parameters may have dual functionality to maintain cellular bioenergetics and cellular health. The tumour cell might maintain these mitochondrial parameters for mitochondrial health or avoid apoptosis, while energy production could be a second priority. This review focuses explicitly on the crosstalk between metabolic domains and the utilisation of these parameters by breast cancer cells for their progression. Some major interventions are discussed based on mitochondrial bioenergetics that need further investigation. This review highlights the pathophysiological significance of mitochondrial bioenergetics and the regulation of its sub-domains by breast tumour cells for uncontrolled proliferation.