Loss of MCU prevents mitochondrial fusion in G₁-S phase and blocks cell cycle progression and proliferation.

ABSTRACT: The role of the mitochondrial Ca²⁺ uniporter (MCU) in physiologic cell proliferation remains to be defined. Here, we demonstrated that the MCU was required to match mitochondrial function to metabolic demands during the cell cycle. During the G₁-S transition (the cycle phase with the highest mitochondrial ATP output), mitochondrial fusion, oxygen consumption, and Ca²⁺ uptake increased in wild-type cells but not in cells lacking MCU. In proliferating wild-type control cells, the addition of the growth factors promoted the activation of the Ca²⁺/calmodulin-dependent kinase II (CaMKII) and the phosphorylation of the mitochondrial fission factor Drp1 at Ser⁶¹⁶ The lack of the MCU was associated with baseline activation of CaMKII, mitochond

SUBMITTER: Koval OM 

PROVIDER: S-EPMC6768401 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature