Search bioRxiv⌕ Search

Biology subjects

Kochan, S. M. V.

Publications and source records attributed to Kochan, S. M. V..

2 recordsLinked to original sources

Enhanced mitochondrial fusion during a critical period of synaptic plasticity in adult-born neurons

Integration of new neurons into adult hippocampal circuits is a process coordinated by local and long-range synaptic inputs. To achieve stable integration and uniquely contribute to hippocampal function, immature neurons are endowed with a critical period of heightened synaptic plasticity, yet it remains unclear which mechanisms sustain this form of plasticity during neuronal maturation. We found that, as new neurons enter their critical period, a transient surge in fusion dynamics stabilizes elongated mitochondrial morphologies in dendrites to fuel synaptic plasticity. Conditional ablation of fusion dynamics to prevent mitochondrial elongation selectively impaired spine plasticity and synaptic potentiation, disrupting neuronal competition for stable circuit integration, ultimately leading to decreased survival. Despite profuse mitochondrial fragmentation, manipulation of competition dynamics was sufficient to restore neuronal survival, but left neurons poorly responsive to experiences at the circuit level. Thus, by enabling synaptic plasticity during the critical period, mitochondrial fusion facilitates circuit remodeling by adult-born neurons.

neuroscience↗

Metabolic control of adult neural stem cell self-renewal by the mitochondrial protease YME1L

The transition between quiescence and activation in neural stem and progenitor cells (NSPCs) is coupled to reversible changes in energy metabolism with key implications for life-long NSPC self-renewal and neurogenesis. How this metabolic plasticity is ensured between NSPC activity states is unclear. We found that a state-dependent rewiring of the mitochondrial proteome by the peptidase YME1L is required to preserve NSPC self-renewal in the adult brain. YME1L-mediated proteome rewiring regulates the rate of fatty acid oxidation (FAO) for replenishing Krebs cycle intermediates and dNTP precursors, which are required to sustain NSPC amplification. Yme1l deletion irreversibly shifts the metabolic profile of NSPCs away from a FAO-dependent state resulting in defective self-renewal, premature differentiation and NSPC pool depletion. Our results disclose an important role for YME1L in coordinating the switch between metabolic states of NSPCs and suggest that NSPC fate is regulated by compartmentalized changes in protein network dynamics.

neuroscience↗