Mitochondrial Quality Measures in the Regulation of Tumor Progression and Metastasis

Mitochondria are positioned as a crucial cell organelle with many decisive functions. Both the lifesaving energy requirement of a cell and cell death initiation are under mitochondria’s control. Because opposing functions are conserved in the same organelle, a tight regulatory mechanism exists in every cell to ensure mitochondrial homeostasis. Any defect in mitochondrial homeostasis contributes to diseases including cancer, neurodegeneration, and cardiovascular disease. In general, mitochondrial functions and homeostasis are maintained through integrated events involving fission, fusion, mitochondrial biogenesis, and mitophagy. Defects in any of these mitochondrial functions contribute to its ability to manage a cell’s energy needs, cellular redox, and metabolic changes. Because of this, mitochondrial regulation of tumor initiation, progression, metastasis, and drug resistance is receiving increased attention from academia, industry, and clinical settings. The recent findings reveal that both inherent and acquired drug resistance against chemotherapy and radiotherapy are primarily governed by mitochondrial structural and functional alterations. Many reviews explain the defective mitochondrial apoptosis as the leading factor of chemotherapeutic resistance, governed by overexpression of antiapoptotic proteins or downregulation of proapoptotic proteins. Similarly, a number of reviews illustrate multiple mitochondrial quality measures and their impact on health and disease. This review primarily focuses on how the standard mitochondrial quality measures and pathways of mitochondrial dynamics regulate cell death decisions culminating in chemotherapeutics resistance, cancer progression, and metastasis. The recent identification of druggable intermediates targeting mitochondrial bioenergetics, fission–fusion, mitobiogenesis, and mitophagy offer great potential to tackle the clinical problems of drug resistance and metastasis.