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Publication : Calcineurin Links Mitochondrial Elongation with Energy Metabolism.

First Author  Pfluger PT Year  2015
Journal  Cell Metab Volume  22
Issue  5 Pages  838-50
PubMed ID  26411342 Mgi Jnum  J:273407
Mgi Id  MGI:6285381 Doi  10.1016/j.cmet.2015.08.022
Citation  Pfluger PT, et al. (2015) Calcineurin Links Mitochondrial Elongation with Energy Metabolism. Cell Metab 22(5):838-50
abstractText  Canonical protein phosphatase 3/calcineurin signaling is central to numerous physiological processes. Here we provide evidence that calcineurin plays a pivotal role in controlling systemic energy and body weight homeostasis. Knockdown of calcineurin in Drosophila melanogaster led to a decrease in body weight and energy stores, and increased energy expenditure. In mice, global deficiency of catalytic subunit Ppp3cb, and tissue-specific ablation of regulatory subunit Ppp3r1 from skeletal muscle, but not adipose tissue or liver, led to protection from high-fat-diet-induced obesity and comorbid sequelae. Ser637 hyperphosphorylation of dynamin-related protein 1 (Drp1) in skeletal muscle of calcineurin-deficient mice was associated with mitochondrial elongation into power-cable-shaped filaments and increased mitochondrial respiration, but also with attenuated exercise performance. Our data suggest that calcineurin acts as highly conserved pivot for the adaptive metabolic responses to environmental changes such as high-fat, high-sugar diets or exercise.
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