Extracellular Vesicle-Mediated Mitochondrial Reprogramming in Cancer

SIMPLE SUMMARY: Mitochondria are important organelles involved in several key cellular processes including energy production and cell death regulation. For this reason, it is unsurprising that mitochondrial function and structure are altered in several pathological states including cancer. Cancer cells present variate strategies to generate sufficient energy to sustain their high proliferation rates. These adaptative strategies can be mediated by extracellular signals such as extracellular vesicles. These vesicles can alter recipient cellular behavior by delivering their molecular cargo. This review explores the different EV-mediated mitochondrial reprogramming mechanisms supporting cancer survival and progression. ABSTRACT: Altered metabolism is a defining hallmark of cancer. Metabolic adaptations are often linked to a reprogramming of the mitochondria due to the importance of these organelles in energy production and biosynthesis. Cancer cells present heterogeneous metabolic phenotypes that can be modulated by signals originating from the tumor microenvironment. Extracellular vesicles (EVs) are recognized as key players in intercellular communications and mediate many of the hallmarks of cancer via the delivery of their diverse biological cargo molecules. Firstly, this review introduces the most characteristic changes that the EV-biogenesis machinery and mitochondria undergo in the context of cancer. Then, it focuses on the EV-driven processes which alter mitochondrial structure, composition, and function to provide a survival advantage to cancer cells in the context of the hallmarks of cancers, such as altered metabolic strategies, migration and invasiveness, immune surveillance escape, and evasion of apoptosis. Finally, it explores the as yet untapped potential of targeting mitochondria using EVs as delivery vectors as a promising cancer therapeutic strategy.