Ost 2015 Abstract IOC100

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Ost M (2015) “Mitokines” and the organismal role of mitochondrial function in energy homeostasis & metabolism. Mitochondr Physiol Network 20.01.

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Ost M (2015)

Event: IOC100

Recent studies have expanded our view of mitochondria beyond their cell autonomous roles, showing that an impaired mitochondrial function in one tissue (e.g. skeletal muscle) has strong metabolic consequences for the whole organism.

To identify key molecular mechanisms in response to chronic mitochondrial distress, we studied transgenic mice with ectopic expression of uncoupling protein 1 in skeletal muscle (UCP1-TG), as a model of muscle-specific mitochondrial perturbation. Ex vivo analysis of functional respiratory capacity performed on permeabilized Soleus muscle fibers revealed an elevated LEAK control ratio and reduced OXPHOS coupling efficiency in transgenic muscles. However, this compromised mitochondrial function promotes an increased total energy expenditure, delayed diet-induced obesity development, improved glucose homeostasis, and even longevity. The exact physiological mechanisms underlying this metabolic improvement have not yet been resolved.

Strikingly, we were able to show that impaired mitochondrial respiratory capacity affects not only muscle itself, but also white adipose tissues (WATs), which show an increased metabolic activity (including mitochondrial COX activity and browning). This suggests a cross-talk between muscle and WAT, possibly mediated by myokines. Very recently, we were able to proof an increased expression and secretion of muscle fibroblast growth factor 21 (FGF21) in UCP1-TG mice. FGF21 has emerged as an important regulator of whole body metabolic processes and its secretion from muscle seems to be related to mitochondrial function, thereby the term “mitokine” has been proposed. Therefore, we conclude that the metabolic improvements of UCP1-TG mice are linked to endocrine effects of FGF21 as a “mitokine” that signals mitochondrial distress to the whole organism in a cell non-autonomous manner, which will be addressed in future studies.


O2k-Network Lab: DE Nuthetal Klaus S


Labels: MiParea: mt-Medicine, mt-Awareness 


Organism: Mouse  Tissue;cell: Skeletal muscle, Fibroblast  Preparation: Permeabilized tissue 


Coupling state: LEAK, OXPHOS 

HRR: Oxygraph-2k 


Affiliations

DIfE Potsdam-Rehbrücke, Germany. - Mario.Ost@dife.de