Skip to main content

Regulation of neuronal connectivity and plasticity by activity-dependent mitochondrial trafficking to synapses

Objective

Regulated trafficking of mitochondria is essential for providing ATP at the correct spatial location to power neural computation, and for providing calcium buffering at sites of calcium entry or release. In neurons, the concentration of mitochondria in specific regions such as growth cones and synapses is important for correct neuronal function and development. Moreover mutations in proteins regulating mitochondrial trafficking compromise neuronal development and the formation, function and plasticity of synapses, and defective mitochondrial trafficking is increasingly implicated in neurological diseases. Understanding the molecular mechanisms that allow neurons to tailor the distribution of mitochondria to changes in neuronal activity therefore has important implications for our understanding of neuronal function and communication. This proposal will study the mechanisms that control the trafficking of the energy providing mitochondria within neurons, and how this relates to neuronal connectivity and plasticity. Using imaging, electrophysiological, molecular and cell biological techniques, combined with viral transduction and mouse transgenic approaches we will determine the molecular mechanisms underlying the activity-dependent subcellular positioning of mitochondria in neurons. We will examine how the mitochondrial Ca2+-sensing GTPases Miro1 and Miro2 act to regulate mitochondrial movement, distribution and function and how this contributes to neuronal development, synaptogenesis and synaptic plasticity. A key goal will be to determine if different roles exist for constitutive versus activity-dependent control of mitochondrial transport by Miro1 and Miro2 in these processes. These studies will significantly advance our understanding of the molecular mechanisms that control mitochondrial localisation in neurons and the role that activity-dependent mitochondrial trafficking plays in regulating neuronal development, morphogenesis, connectivity and function.

Field of science

  • /natural sciences/chemical sciences/inorganic chemistry/inorganic compounds

Call for proposal

ERC-2011-StG_20101109
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

University College London
Address
Gower Street
WC1E 6BT London
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 997 567
Principal investigator
Josef Kittler (Dr.)
Administrative Contact
Giles Machell (Mr.)

Beneficiaries (1)

University College London
United Kingdom
EU contribution
€ 1 997 567
Address
Gower Street
WC1E 6BT London
Activity type
Higher or Secondary Education Establishments
Principal investigator
Josef Kittler (Dr.)
Administrative Contact
Giles Machell (Mr.)