Restoration of mitochondria function as a target for cancer therapy

•Mitochondria dysfunction is a key reason for therapy resistance in cancer.•Defective oxidative phosphorylation contributes to mitochondria dysfunction.•Heat shock proteins and dichloroacetate restore mitochondria function.•Restoration of mitochondria function induces apoptosis in cancer cells.•Dichloroacetate exerts anticancer effects via multiple mechanisms of action. Defective oxidative phosphorylation has a crucial role in the attenuation of mitochondrial function, which confers therapy resistance in cancer. Various factors, including endogenous heat shock proteins (HSPs) and exogenous agents such as dichloroacetate, restore respiratory and other physiological functions of mitochondria in cancer cells. Functional mitochondria might ultimately lead to the restoration of apoptosis in cancer cells that are refractory to current anticancer agents. Here, we summarize the key reasons contributing to mitochondria dysfunction in cancer cells and how restoration of mitochondrial function could be exploited for cancer therapeutics.