The Mitochondrial Proteome of Tumor Cells: A SnapShot on Methodological Approaches and New Biomarkers

Simple Summary Mitochondria are central hubs of cellular signaling, energy metabolism, and redox balance. The plasticity of these cellular organelles is an essential requisite for the cells to cope with different stimuli and stress conditions. Cancer cells are characterized by changes in energy metabolism, mitochondrial signaling, and dynamics. These changes are driven by alterations in the mitochondrial proteome. For this reason, in the last years a focus of basic and cancer research has been the implementation and optimization of technologies to investigate changes in the mitochondrial proteome during cancer initiation and progression. This review presents an overview of the most used technologies to investigate the mitochondrial proteome and recent evidence on changes in the expression levels and delocalization of certain proteins in and out the mitochondria for shaping the functional properties of tumor cells. Mitochondria are highly dynamic and regulated organelles implicated in a variety of important functions in the cell, including energy production, fatty acid metabolism, iron homeostasis, programmed cell death, and cell signaling. Changes in mitochondrial metabolism, signaling and dynamics are hallmarks of cancer. Understanding whether these modifications are associated with alterations of the mitochondrial proteome is particularly relevant from a translational point of view because it may contribute to better understanding the molecular bases of cancer development and progression and may provide new potential prognostic and diagnostic biomarkers as well as novel molecular targets for anti-cancer treatment. Making an inventory of the mitochondrial proteins has been particularly challenging given that there is no unique consensus targeting sequence that directs protein import into mitochondria, some proteins are present at very low levels, while other proteins are expressed only in some cell types, in a particular developmental stage or under specific stress conditions. This review aims at providing the state-of-the-art on methodologies used to characterize the mitochondrial proteome in tumors and highlighting the biological relevance of changes in expression and delocalization of proteins in and out the mitochondria in cancer biology.