Wright 2013 Abstract MiP2013
|Wright L, Rizzuto R (2013) Calcium regulation of metabolism in adipocytes. Mitochondr Physiol Network 18.08.|
Calcium (Ca2+) is an important intracellular signalling molecule in mammalian tissues, and has been associated with the regulation of diverse processes, including contraction, secretion, autophagy, ion pumping, and the activation of metabolic enzymes. Mitochondria maintain a calcium gradient between the matrix and the cytoplasm, via the actions of specific transporters in the inner mitochondrial membrane. Under conditions of metabolic dysfunction (such as insulin resistance), mitochondrial calcium homeostasis is often altered (for a recent review, see ).
With the recent identification of the mitochondrial calcium uniporter (MCU) and associated regulatory proteins, as well as the use of targeted aequorin probes, we are now able to investigate the role of mitochondrial Ca2+ in the regulation of whole-cell adipocyte metabolism [2,3]. Preliminary data suggest that the induction of insulin resistance (by treatment with 100 nM insulin for 24 h) in cultured adipocytes alters the expression of key components of the uniporter (+75% MCUa and +42% MCUb compared to control, P<0.05), and increases Ca2+ uptake into the mitochondria (+76%, P<0.05). Similarly, feeding mice a high-fat-high-sugar diet alters the expression of these genes in visceral white adipose tissue (+54% MCUa and +127% MCUb compared to chow-fed control, P<0.05). Additionally, we saw that direct manipulation of mitochondrial calcium by overexpression of MCUb in cultured adipocytes was able to alter a number of metabolic parameters, including mitochondrial membrane potential, NADH dynamics, and the rate of glucose oxidation. The mechanism and significance of these metabolic alterations is currently under investigation.
We theorise that mitochondrial calcium plays an important role in the orchestration of metabolic homeostasis in adipocytes. As such, the MCU may represent an interesting node of metabolic regulation - and therefore therapeutic potential - in times of metabolic dysregulation.
Labels: MiParea: Respiration, Genetic knockout;overexpression, Exercise physiology;nutrition;life style Pathology: Diabetes
Organism: Mouse Tissue;cell: Fat, Other cell lines Preparation: Intact cells
Regulation: Calcium, Ion;substrate transport, mt-Membrane potential Coupling state: ROUTINE
Dept of Biological Sciences, University of Padua, Italy. - Email: email@example.com
- Patron M, Raffaello A, Granatiero V, Tosatto A, Merli G, De Stefani D, Wright L, Pallafacchina G, Terrin A, Mammucari C, Rizzuto R (2013) The mitochondrial calcium uniporter (MCU): Molecular identity and physiological roles. J Biol Chem 288: 10750-10758.
- Baughman JM, Perocchi F, Girgis HS, Plovanich M, Belcher-Timme CA, Sancak Y, Bao, XR, Strittmatter L, Goldberger O, Bogorad RL, Koteliansky V, Mootha VK (2011) Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 476: 341-345.
- De Stefani D, Raffaello A, Teardo E, Szabo I, Rizzuto R (2011) A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 476: 336-340.