“The Loss of Golden Touch”: Mitochondria-Organelle Interactions, Metabolism, and Cancer

Abstract

Mitochondria represent the energy hub of cells and their function is under the constant influence of their tethering with other subcellular organelles. Mitochondria interact with the endoplasmic reticulum, lysosomes, cytoskeleton, peroxisomes, and nucleus in several ways, ranging from signal transduction, vesicle transport, and membrane contact sites, to regulate energy metabolism, biosynthetic processes, apoptosis, and cell turnover. Tumorigenesis is often associated with mitochondrial dysfunction, which could likely be the result of an altered interaction with different cell organelles or structures. The purpose of the present review is to provide an updated overview of the links between inter-organellar communications and interactions and metabolism in cancer cells, with a focus on mitochondria. The very recent publication of several reviews on these aspects testifies the great interest in the area. Here, we aim at (1) summarizing recent evidence supporting that the metabolic rewiring and adaptation observed in tumors deeply affect organelle dynamics and cellular functions and vice versa; (2) discussing insights on the underlying mechanisms, when available; and (3) critically presenting the gaps in the field that need to be filled, for a comprehensive understanding of tumor cells’ biology. Chemo-resistance and druggable vulnerabilities of cancer cells related to the aspects mentioned above is also outlined.

Inhibition of PI3K/AKT signaling via ROS regulation is involved in Rhein-induced apoptosis and enhancement of oxaliplatin sensitivity in pancreatic cancer cells

“…As shown in Figure 2B, the percentage of apoptotic Panc-1 and MIAPaca-2 cells increased in a dose-dependent manner after Rhein treatment. Considering the important role of mitochondria in cell survival and apoptosis [20], we analyzed the mitochondrial transmembrane potential (Δψm) by JC-1 staining. Rhein treatment resulted in a dose-dependent loss of Δψm, which is associated with mitochondria dysfunction and apoptosis (Figure 2C).…”

The Interplay between Dysregulated Ion Transport and Mitochondrial Architecture as a Dangerous Liaison in Cancer

“…They participate in the integration and modulation of the response to such signals, not only through adapting energy production and consumption, but also by playing key roles in signaling, cell cycle progression, cell motility, cell fate decisions, and by coordinating adaptive strategies with other cellular structures. As such, they engage in direct interactions with the endoplasmic reticulum (ER), trans-Golgi network, lysosomes, lipid droplets, peroxisomes, and the plasma membrane, and are embedded in—and interact with—a dynamically regulated cytoskeletal network [ 2 , 3 ]. Therefore, it is not surprising that the pervasive phenotypical changes occurring during cancer development profoundly impact mitochondrial architecture and function and that this, in turn, plays a key role in the cancer cell phenotype.…”

Insulin and Its Key Role for Mitochondrial Function/Dysfunction and Quality Control: A Shared Link between Dysmetabolism and Neurodegeneration

“…Mitochondria are interconnected organelles that play a critical role in various cellular processes, including: ATP production by oxidative phosphorylation (OXPHOS), metabolite biosynthesis, intracellular calcium buffering and signaling, ROS generation, steroidogenesis, immune responses, β-oxidation of fatty acids, modification of phospholipids, apoptosis, and stem cell reprogramming [ 127 ].…”