RT Journal Article
SR Electronic
T1 Metabolic control of adult neural stem cell self-renewal by the mitochondrial protease YME1L
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.08.18.456709
DO 10.1101/2021.08.18.456709
A1 Gulzar A. Wani
A1 Hans-Georg Sprenger
A1 Kristiano Ndoci
A1 Srikanth Chandragiri
A1 Richard James Acton
A1 Désirée Schatton
A1 Sandra M.V. Kochan
A1 Vignesh Sakthivelu
A1 Milica Jevtic
A1 Jens M. Seeger
A1 Stefan Müller
A1 Patrick Giavalisco
A1 Elena I. Rugarli
A1 Elisa Motori
A1 Thomas Langer
A1 Matteo Bergami
YR 2021
UL http://biorxiv.org/content/early/2021/08/19/2021.08.18.456709.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.