Completed Brain & Nervous System Cells, Biochemistry & Physiology

Mitochondrial dynamics in CNS health and disease

Funder Wellcome Charity-funded
Recipient organisation University College London
Funding £1.9M
Period Jun 2021 — May 2026

In plain English

AI plain-English summary

Brain cells must precisely position their mitochondria—the tiny power plants inside them—to deliver energy exactly where it is needed for signalling and to mop up excess calcium that could otherwise damage them. This project investigates how the internal scaffolding of neurons and glial cells coordinates the movement, anchoring, and reshaping of mitochondria, and what happens when that coordination fails. The problem is that while scientists know mitochondrial dysfunction is linked to neurodegenerative diseases such as Parkinson’s and Alzheimer’s, the molecular machinery that controls where mitochondria go and how they behave inside brain cells remains poorly understood. Without that knowledge, it is impossible to design therapies that target the root cause rather than just symptoms. This is fundamental science. If successful, it will reveal the specific roles of Miro proteins in linking mitochondrial transport to electrical activity, and show how disrupted mitochondrial dynamics drive synapse loss and neuronal death. That mechanistic understanding could eventually point toward drug targets for conditions where energy supply in the brain goes awry. Past fundamental work on mitochondrial transport has already informed treatments for rare mitochondrial disorders, so the payoff here is likely to be conceptual clarity first, clinical application later.

View original technical description
The tight regulation of mitochondrial transport and anchoring in brain cells is essential for providing ATP at the correct spatial location to power neural function and computation, and for providing calcium buffering at sites of calcium entry or release. Using a multidisciplinary approach, combining imaging, biochemistry, electrophysiology and mouse transgenics we will determine the molecular and cellular mechanisms by which the cytoskeleton coordinates mitochondrial transport, localisation and remodelling in neurons and glial cells. The influence of this regulation on the development and maintenance of neuronal connectivity, function, plasticity and pathology will then be determined in vitro and in vivo. The main objectives are to define (i) the role of Miro proteins as central coordinators of the activity-dependent transport, positioning and remodelling of mitochondria through the microtubule, actin and septin cytoskeletons; (ii) how mitochondrial position and calcium buffering in neurons and glia impacts the formation, maintenance and plasticity of synapses; and (iii) the mechanisms by which disrupted mitochondrial dynamics lead to neuronal pathology and neurodegeneration. Our proposal will provide unique insight into how mitochondrial networks in neurons and astrocytes contribute to regulating the operation and plasticity of synapses and how their disruption leads to neuronal pathology in brain diseases.

View the original record at the funder ↗

Researchers

Josef Kittler (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Miro dependent mitochondrial dynamics and the regulation of neuronal migration
Activity-dependent trafficking of mitochondria to synapses by Miro1.
New insights into mitochondrial dynamics and quality control
MIRO interaction mapping for neuronal mitochondrial dynamics
Regulation and resilience of the neuronal microtubule cytoskeleton in health and disease

Original classification

Investigator Award in Science

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.