Molecular Physiology of Synaptic Bioenergetics (Chaire Diane Barrière)

Mitochondria, intracellular organelles, play a major role in neuronal functions, controlling 3 fundamental and essential mechanisms of neurobiology and synaptic transmission:
 

• ATP (Adenosine-TriPhosphate) Production
• Calcium homeostasis
• Cell death by apoptosis
   

Using advanced optical technologies to study bioenergetics of active synapses in combination with targeted manipulations of metabolism and genetics, the team will unravel the molecular mechanisms by which synaptic mitochondria control normal and pathological neuronal function. The objectives of this work are to:

• To better understand the neurophysiological role of mitochondria in synaptic metabolic integrity
• To strengthen the understanding of the relationship between mitochondrial dysfunction and metabolic epilepsy
• To provide a basis for future studies to improve mitochondrial bioenergetics in mitochondrial neurological diseases

Ashrafi, G.*, de Juan-Sanz, J*, Farrell, R.J. and Ryan T.A. (2020). Molecular tuning of the axonal mitochondrial Ca2+ uniporter ensures metabolic flexibility of neurotransmission. Neuron, 105(4):678-687.e5. * Co-first authors.

De la Rocha-Muñoz, A., Núñez, E., Gómez-López, S., López-Corcuera B., de Juan-Sanz J* and Aragón C (2020). The presynaptic glycine transporter GlyT2 is regulated by the Hedgehog pathway in vitro and in vivo. * Corresponding author. BioRxiv.doi:https://doi. org/10.1101/2020.07.28.224659.

De la Rocha-Muñoz A., Núñez, E., Arribas-González, E., López Corcuera,B., Aragón, C* and de Juan-Sanz J* (2019). E3 ubiquitin ligases LNX1 and LNX2 are major regulators of the presynaptic glycine transporter GlyT2. * Co-corresponding authors. Scientific Reports. Sci Rep 9, 14944

Koopmans F, van Nierop P, Andres-Alonso M, (…) Malenka R, Nicoll RA, Pulido C, de Juan-Sanz J, Sheng M, Südhof TC, (…) Thomas PD, Smit AB, Verhage M (2019). SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse. Neuron, 103(2):217-234

De Juan-Sanz, J., Holt, G. T., Schreiter, E. R., de Juan, F., Kim, D. S., & Ryan, T. A. (2017). Axonal endoplasmic reticulum Ca 2+ content controls release probability in CNS nerve terminals. Neuron, 93(4), 867-881