Mitochondrial Function

Group Head: Andreas Wiederkehr, Ph.D. Contact


Mitochondrial dysfunction is one of the main underlying causes of chronic diseases such as metabolic syndrome, type 2 diabetes and neurodegenerative diseases. In addition, mitochondrial function declines with age. The mission of the Mitochondrial Function group is to develop methods to assess mitochondrial function and apply them to the study of chronic diseases and aging. The group focuses on mitochondrial signalling events that adapt energy metabolism to the hormonal and nutrient status of the cell. These control mechanisms can be exploited to identify nutrients and bioactives that prevent mitochondrial dysfunction in specific tissues as a result of diseases progression or aging. Our group is using live-cell imaging, basic biochemistry and proteomics to study mitochondrial function.

Key Goals

  • Deliver methods for the study of mitochondrial function.
  • Identify nutritional approaches that improve mitochondrial function and slow chronic disease processes in the ageing population.
  • Provide novel evidence linking nutrients to the regulation of mitochondrial activity.
  • Develop research on mitochondrial signal transduction in neurons, astrocytes and pancreatic beta-cells.

 

Key Publications of the Group*

Santo-Domingo J, Chareyron I, Dayon L, Núñez Galindo A, Cominetti O, Pilar Giner Giménez M, De Marchi U, Canto C, Kussmann M, Wiederkehr A. (2017) Coordinated activation of mitochondrial respiration and exocytosis mediated by PKC signaling in pancreatic b-cells. FASEB J. 31(3):1028-1045.

Thevenet J, De Marchi U, Domingo JS, Christinat N, Bultot L, Lefebvre G, Sakamoto K, Descombes P, Masoodi M, Wiederkehr A. (2016) Medium-chain fatty acids inhibit mitochondrial metabolism in astrocytes promoting astrocyte-neuron lactate and ketone body shuttle systems. FASEB J. 30(5):1913-26.

De Marchi U, Thevenet J, Hermant A, Dioum E, Wiederkehr A. (2014) Calcium co-regulates oxidative metabolism and ATP synthase-dependent respiration in pancreatic beta cells. J Biol Chem. 289(13):9182-94.

Quan X, Nguyen TT, Choi SK, Xu S, Das R, Cha SK, Kim N, Han J, Wiederkehr A, Wollheim CB, Park KS. (2015) Essential role of mitochondrial Ca2+ uniporter in the generation of mitochondrial pH gradient and metabolism-secretion coupling in insulin-releasing cells. J Biol Chem. 290(7):4086-96.

Wiederkehr A, Wollheim CB. (2012) Mitochondrial signals drive insulin secretion in the pancreatic β-cell. Mol Cell Endocrinol. 353(1-2):128-37.