Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.17 (
CaMKII
)
4,029
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The role of the mitochondrial Ca
2+
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 G
1
-S transition (the cycle phase with the highest mitochondrial ATP output), mitochondrial fusion, oxygen consumption, and Ca
2+
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 Ca
2+
/
calmodulin-dependent kinase II
(
CaMKII
) and the phosphorylation of the
mitochondrial fission factor
Drp1 at Ser
616
The lack of the MCU was associated with baseline activation of
CaMKII
, mitochondrial fragmentation due to increased Drp1 phosphorylation, and impaired mitochondrial respiration and glycolysis. The mitochondrial fission/fusion ratio and proliferation in MCU-deficient cells recovered after MCU restoration or inhibition of mitochondrial fragmentation or of
CaMKII
in the cytosol. Our data highlight a key function for the MCU in mitochondrial adaptation to the metabolic demands during cell cycle progression. Cytosolic
CaMKII
and the MCU participate in a regulatory circuit, whereby mitochondrial Ca
2+
uptake affects cell proliferation through Drp1.
...
PMID:Loss of MCU prevents mitochondrial fusion in G
1
-S phase and blocks cell cycle progression and proliferation. 3104 Feb 60
