Canto 2019 MiP2019

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Carles Canto Alvarez
Mitochondrial dynamics and cellular metabolism: lessons from mouse models.

Link: MiP2019

Valera-Alberni M, Boutant M, Kulkarni SS, Joffraud M, Sanchez Garcia JL, Canto C (2019)

Event: MiP2019

COST Action MitoEAGLE

Mitochondrial dysfunction is a hallmark for multiple metabolic and age-related diseases [1]. Mitochondrial quality control mechanisms are largely influenced by mitochondrial fusion and fission events, referred to as mitochondrial dynamics, which also influence mitochondrial bioenergetics properties [2]. Nevertheless most of this knowledge derives from the use of cultured cell lines, and the role of different mitochondrial fusion and fission regulators in differentiated tissues remains unclear.

In order to explore the role of Mitofusins (Mfn1 and Mfn2) and Drp1 in tissue metabolism, we have generated a collection of conditional, tissue-specific, mouse models for defective fusion and fission mechanisms. Further, we have examined how these mice respond to dietary (e.g.: high-fat feeding) and physiological challenges. We will have a special focus on their impact on brown adipose tissue metabolism and thermogenesis.

Our results illustrate the Mfn1 and Mfn2, despite being both involved in mitochondrial fusion, have critically different roles in brown adipose tissue physiology. In particular, Mfn2 plays a unique role in linking mitochondria to lipid droplets. We will also discuss how Drp1 phosphorylation impacts mitochondrial fusion/fission in brown adipose tissue by using phospho-null knockin mice.

As a whole, our results illustrate that mitochondrial dynamics-related proteins critically influence thermogenic capacity and energy substrate utilization in brown adipose tissue. In addition, we show that this occurs not just through the modulation of mitochondrial architecture, but also by enabling the communication of mitochondria with other cellular organelles.


Bioblast editor: Plangger M, Tindle-Solomon L O2k-Network Lab: CH Lausanne Canto C


Labels: MiParea: mt-Structure;fission;fusion 


Organism: Mouse  Tissue;cell: Fat 





Affiliations

Valera-Alberni M(1,2), Boutant M(1), Kulkarni SS(1), Joffraud M(1) and Sanchez Garcia JL(1) and Canto C(1,2)
  1. Nestlé Inst Health Sciences (NIHS), EPFL Innovation Park
  2. School Life Sciences, EPFL, Lausanne; Switzerland. - [email protected]

References

  1. Liesa M, Shirihai O (2013) Mitochondrial dynamics in the regulation of nutrient utilization and energy expenditure. Cell Metab 17:491-506.
  2. Canto C (2018) Mitochondrial dynamics: shaping metabolic adaptation. Int Rev Cell Mol Biol 340:129-67.