Early dysregulation of GSK3β impairs mitochondrial activity in Fragile X Syndrome DOI Creative Commons

Giulia Cencelli,

G Pedini,

Claudia Ricci

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 203, P. 106726 - 106726

Published: Nov. 5, 2024

The finely tuned regulation of mitochondria activity is essential for proper brain development. Fragile X Syndrome (FXS), the leading cause inherited intellectual disability, a neurodevelopmental disorder in which mitochondrial dysfunction has been increasingly implicated. This study investigates role Glycogen Synthase Kinase 3β (GSK3β) FXS. Several studies have reported dysregulation GSK3β FXS, and its function also well established. However, link between disrupted FXS remains unexplored. Utilizing Fmr1 knockout (KO) mice human cell lines from individuals with we uncovered developmental window where dysregulated disrupts function. Notably, partial inhibition fibroblasts young rescues observed defects, suggesting that targeting early stages may offer therapeutic benefits this condition.

Language: Английский

FMRP regulates MFF translation to locally direct mitochondrial fission in neurons DOI Creative Commons
Adam R. Fenton, Ruchao Peng, Charles Bond

et al.

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(12), P. 2061 - 2074

Published: Nov. 15, 2024

Fragile X messenger ribonucleoprotein (FMRP) is a critical regulator of translation, whose dysfunction causes fragile syndrome. FMRP disrupts mitochondrial health in neurons, but it unclear how supports homoeostasis. Here we demonstrate that granules are recruited to the midzone, where they mark fission sites axons and dendrites. Endolysosomal vesicles contribute granule positioning around mitochondria facilitate FMRP-associated via Rab7 GTP hydrolysis. Cryo-electron tomography real-time translation imaging reveal mitochondria-associated ribosome-rich structures serve as local protein synthesis. Specifically, promotes factor (MFF), selectively enabling replicative at midzone. Disrupting function dysregulates MFF perturbs dynamics, resulting increased peripheral an irregular distribution nucleoids. Thus, regulates precise control fission.

Language: Английский

Citations

5
Early dysregulation of GSK3β impairs mitochondrial activity in Fragile X Syndrome DOI Creative Commons

Giulia Cencelli,

G Pedini,

Claudia Ricci

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 203, P. 106726 - 106726

Published: Nov. 5, 2024

The finely tuned regulation of mitochondria activity is essential for proper brain development. Fragile X Syndrome (FXS), the leading cause inherited intellectual disability, a neurodevelopmental disorder in which mitochondrial dysfunction has been increasingly implicated. This study investigates role Glycogen Synthase Kinase 3β (GSK3β) FXS. Several studies have reported dysregulation GSK3β FXS, and its function also well established. However, link between disrupted FXS remains unexplored. Utilizing Fmr1 knockout (KO) mice human cell lines from individuals with we uncovered developmental window where dysregulated disrupts function. Notably, partial inhibition fibroblasts young rescues observed defects, suggesting that targeting early stages may offer therapeutic benefits this condition.

Language: Английский

Citations

1