Creatine kinase B controls futile creatine cycling in thermogenic fat.

Autor: Rahbani JF; Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.; Department of Biochemistry, McGill University, Montreal, Quebec, Canada., Roesler A; Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.; Department of Biochemistry, McGill University, Montreal, Quebec, Canada., Hussain MF; Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.; Department of Biochemistry, McGill University, Montreal, Quebec, Canada., Samborska B; Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.; Department of Biochemistry, McGill University, Montreal, Quebec, Canada., Dykstra CB; Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.; Department of Biochemistry, McGill University, Montreal, Quebec, Canada., Tsai L; Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Jedrychowski MP; Dana-Farber Cancer Institute, Department of Cell Biology, Harvard Medical School, Boston, MA, USA., Vergnes L; Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA., Reue K; Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA., Spiegelman BM; Dana-Farber Cancer Institute, Department of Cell Biology, Harvard Medical School, Boston, MA, USA., Kazak L; Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada. lawrence.kazak@mcgill.ca.; Department of Biochemistry, McGill University, Montreal, Quebec, Canada. lawrence.kazak@mcgill.ca.
Jazyk: angličtina
Zdroj: Nature [Nature] 2021 Feb; Vol. 590 (7846), pp. 480-485. Date of Electronic Publication: 2021 Feb 17.
DOI: 10.1038/s41586-021-03221-y
Abstrakt: Obesity increases the risk of mortality because of metabolic sequelae such as type 2 diabetes and cardiovascular disease 1 . Thermogenesis by adipocytes can counteract obesity and metabolic diseases 2,3 . In thermogenic fat, creatine liberates a molar excess of mitochondrial ADP-purportedly via a phosphorylation cycle 4 -to drive thermogenic respiration. However, the proteins that control this futile creatine cycle are unknown. Here we show that creatine kinase B (CKB) is indispensable for thermogenesis resulting from the futile creatine cycle, during which it traffics to mitochondria using an internal mitochondrial targeting sequence. CKB is powerfully induced by thermogenic stimuli in both mouse and human adipocytes. Adipocyte-selective inactivation of Ckb in mice diminishes thermogenic capacity, increases predisposition to obesity, and disrupts glucose homeostasis. CKB is therefore a key effector of the futile creatine cycle.
Databáze: MEDLINE
Externí odkaz: