Mitochondria are the powerhouse organelles present in all eukaryotic cells. They play a fundamental role in cell
respiration, survival and metabolism. Stimulation of G-protein coupled receptors (GPCRs) by dedicated ligands
and consequent activation of the cAMP·PKA pathway finely couple energy production and metabolism to cell
growth and survival. Compartmentalization of PKA signaling at mitochondria by A-Kinase Anchor Proteins
(AKAPs) ensures efficient transduction of signals generated at the cell membrane to the organelles, controlling
important aspects of mitochondrial biology. Emerging evidence implicates mitochondria as essential bioenergetic
elements of cancer cells that promote and support tumor growth and metastasis. In this context, mitochondria
provide the building blocks for cellular organelles, cytoskeleton and membranes, and supply all the
metabolic needs for the expansion and dissemination of actively replicating cancer cells. Functional interference
with mitochondrial activity deeply impacts on cancer cell survival and proliferation. Therefore, mitochondria
represent valuable targets of novel therapeutic approaches for the treatment of cancer patients. Understanding
the biology of mitochondria, uncovering the molecular mechanisms regulating mitochondrial activity andmapping
the relevant metabolic and signaling networks operating in cancer cells will undoubtly contribute to
create a molecular platform to be used for the treatment of proliferative disorders.
Here, we will highlight the emerging roles of signaling pathways acting downstream to GPCRs and their
intersection with the ubiquitin proteasome system in the control of mitochondrial activity in different aspects of
cancer cell biology
