The AKAP1 ribonucleoprotein network integrates mitochondrial homeostasis, P-body dynamics and protein translation in cycling cells

Integration of protein translation and mitochondrial activities represents a mechanism to rapidly adapt anabolic processes to specific cellular needs. This aspect is of particular importance for cell division when mitochondrial dynamics, oxidative phosphorylation and protein synthesis are timely coordinated to allow a faithful completion of cell cycle. However, the mechanisms coupling mitochondrial homeostasis to protein translation in cycling cells are largely unknown. Here, we report the identification of a molecular network assembled by AKAP1 at mitochondria that includes mRNA, components of the translation repression machinery (P-bodies) and mitotic kinases (CDK1/2). During the interphase, the AKAP1 complex dynamically coordinates cAMP signaling, mitochondrial activity, P-body dynamics and protein translation to ensure proper cell cycle progression. At mitosis, CDK-induced proteolysis of AKAP1 via a cullin-mediated ubiquitin pathway reduces oxidative metabolism, promotes mitochondrial fission and reshapes mRNA translation, finalizing the cell cycle. Disruption of this network impairs cell cycle progression. These findings unveil a regulatory mechanism controlled by AKAP1 that functionally and dynamically links oxidative metabolism to protein synthesis in cycling cells. Targeting this biological node could help to restore deranged mitochondrial function in degenerative and proliferative disorders.