Next Article in Journal
Glucose Metabolic Dysfunction in Neurodegenerative Diseases—New Mechanistic Insights and the Potential of Hypoxia as a Prospective Therapy Targeting Metabolic Reprogramming
Previous Article in Journal
Melatonin, Its Beneficial Effects on Embryogenesis from Mitigating Oxidative Stress to Regulating Gene Expression
 
 
Article

Deficits in Prenatal Serine Biosynthesis Underlie the Mitochondrial Dysfunction Associated with the Autism-Linked FMR1 Gene

1
Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA
2
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
3
Medical Sciences Campus, Department of Biochemistry, University of Puerto Rico, San Juan PR00936, Puerto Rico
4
Department of Pediatrics, University of California Davis Medical Center, Sacramento, CA 95817, USA
5
The MIND Institute, University of California Davis Medical Center, Sacramento, CA 95817, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Asher Ornoy
Int. J. Mol. Sci. 2021, 22(11), 5886; https://doi.org/10.3390/ijms22115886
Received: 23 April 2021 / Revised: 25 May 2021 / Accepted: 27 May 2021 / Published: 30 May 2021
(This article belongs to the Section Molecular Neurobiology)
Fifty-five to two hundred CGG repeats (called a premutation, or PM) in the 5′-UTR of the FMR1 gene are generally unstable, often expanding to a full mutation (>200) in one generation through maternal inheritance, leading to fragile X syndrome, a condition associated with autism and other intellectual disabilities. To uncover the early mechanisms of pathogenesis, we performed metabolomics and proteomics on amniotic fluids from PM carriers, pregnant with male fetuses, who had undergone amniocentesis for fragile X prenatal diagnosis. The prenatal metabolic footprint identified mitochondrial deficits, which were further validated by using internal and external cohorts. Deficits in the anaplerosis of the Krebs cycle were noted at the level of serine biosynthesis, which was confirmed by rescuing the mitochondrial dysfunction in the carriers’ umbilical cord fibroblasts using alpha-ketoglutarate precursors. Maternal administration of serine and its precursors has the potential to decrease the risk of developing energy shortages associated with mitochondrial dysfunction and linked comorbidities. View Full-Text
Keywords: amniotic fluid; premutation; CGG repeats; FMR1; metabolomics; proteomics amniotic fluid; premutation; CGG repeats; FMR1; metabolomics; proteomics
Show Figures

Figure 1

MDPI and ACS Style

Nolin, S.L.; Napoli, E.; Flores, A.; Hagerman, R.J.; Giulivi, C. Deficits in Prenatal Serine Biosynthesis Underlie the Mitochondrial Dysfunction Associated with the Autism-Linked FMR1 Gene. Int. J. Mol. Sci. 2021, 22, 5886. https://doi.org/10.3390/ijms22115886

AMA Style

Nolin SL, Napoli E, Flores A, Hagerman RJ, Giulivi C. Deficits in Prenatal Serine Biosynthesis Underlie the Mitochondrial Dysfunction Associated with the Autism-Linked FMR1 Gene. International Journal of Molecular Sciences. 2021; 22(11):5886. https://doi.org/10.3390/ijms22115886

Chicago/Turabian Style

Nolin, Sarah L., Eleonora Napoli, Amanda Flores, Randi J. Hagerman, and Cecilia Giulivi. 2021. "Deficits in Prenatal Serine Biosynthesis Underlie the Mitochondrial Dysfunction Associated with the Autism-Linked FMR1 Gene" International Journal of Molecular Sciences 22, no. 11: 5886. https://doi.org/10.3390/ijms22115886

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop