Dr. Simon Licht-Mayer
Medizinische Universität Wien
Klinisches Institut für Labormedizin
Wien, Austria
Programm
“Mitochondrial function and adaptation in neuronal vulnerability, repair and pain”
Neurons depend on mitochondrial energy production and effective distribution to maintain their extensive processes and respond to injury. Understanding how endogenous mitochondrial adaptations support neuronal survival and regeneration offers opportunities to develop therapies for neurodegeneration, impaired repair and chronic pain.
We previously identified a homeostatic mechanism, termed the axonal response of mitochondria to demyelination (ARMD), through which neurons mobilize mitochondria into demyelinated axons. Enhancing this response protects axons from degeneration, supporting a therapeutic strategy now advancing toward phase II clinical evaluation. We are currently investigating the transcriptional programmes underlying ARMD in the central and peripheral projections of dorsal root ganglion (DRG) neurons, together with its long-term consequences, to determine how this response can be targeted more effectively and sustainably.
Extending this approach to regeneration, we investigate how peripheral conditioning alters mitochondrial function and distribution to support axonal growth. A peripheral conditioning lesion activates an intrinsic adaptive response that can protect the central projections of sensory neurons and enhance their regeneration following spinal cord injury. Our preliminary data implicate mitochondria as important contributors to this conditioning-induced protection, motivating efforts to identify the adaptations that support neuronal resilience and regenerative capacity.
In the context of chronic pain, we demonstrate that DRG neuronal subpopulations exhibit distinct mitochondrial properties at baseline and differ in their susceptibility to mitochondrial perturbation. Selectively affecting particular sensory-neuron populations protects against chronic pain in experimental models, identifying mitochondrial heterogeneity as a potential basis for targeted intervention.
In parallel, we examine how impaired oxidative phosphorylation disrupts mitochondrial turnover and maintenance in vulnerable dopaminergic neurons, particularly within distal axonal compartments. By comparing mitochondrial properties across neuronal populations and following their responses to energy deficiency, we aim to understand why some neurons are especially susceptible to degeneration and whether modifying mitochondrial dynamics can improve their survival.
By defining the mitochondrial mechanisms that support neuronal maintenance and adaptation, we aim to identify opportunities to preserve axons, enhance regeneration and alleviate chronic pain.
Host and contact for questions: Helmut KUBISTA