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The Mitochondrial Aspartate/Glutamate Carrier AGC1 and Calcium Homeostasis: Physiological Links and Abnormalities in Autism

Abstract

Autism spectrum disorder (ASD) is a severe, complex neurodevelopmental disorder characterized by impairments in reciprocal social interaction and communication, and restricted and stereotyped patterns of interests and behaviors. Recent evidence has unveiled an important role for calcium (Ca2+) signaling in the pathogenesis of ASD. Post-mortem studies of autistic brains have pointed toward abnormalities in mitochondrial function as possible downstream consequences of altered Ca2+ signaling, abnormal synapse formation, and dysreactive immunity. SLC25A12, an ASD susceptibility gene, encodes the Ca2+-regulated mitochondrial aspartate–glutamate carrier, isoform 1 (AGC1). AGC1 is an important component of the malate/aspartate shuttle, a crucial system supporting oxidative phosphorylation and adenosine triphosphate (ATP) production. Here, we review the physiological roles of AGC1, its links to calcium homeostasis, and its involvement in autism pathogenesis.

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Acknowledgments

We gratefully acknowledge the Maryland NICHD Brain & Tissue Bank for Developmental Disorders, the Harvard Brain Tissue Resource Center, and the Autism Tissue Program for providing the brain tissue samples assessed in our studies. The Persico Lab is supported by the Italian Ministry for University, Scientific Research and Technology (PRIN n. 2006058195 and 2008BACT54_002), the Italian Ministry of Health (RFPS-2007-5-640174), the Autism Speaks Foundation (Princeton, NJ), the Autism Research Institute (San Diego, CA), the Fondazione Gaetano e Mafalda Luce (Milan, Italy), and Autism Aids Onlus (Naples, Italy). The Palmieri lab is supported by the Italian Ministry for University, Scientific Research and Technology (PRIN n. 2008BACT54_002 and FIRB n. RBIN04PHZ7_001).

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We declare no conflict of interest.

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Correspondence to Antonio M. Persico or Luigi Palmieri.

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Napolioni, V., Persico, A.M., Porcelli, V. et al. The Mitochondrial Aspartate/Glutamate Carrier AGC1 and Calcium Homeostasis: Physiological Links and Abnormalities in Autism. Mol Neurobiol 44, 83–92 (2011). https://doi.org/10.1007/s12035-011-8192-2

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  • DOI: https://doi.org/10.1007/s12035-011-8192-2

Keywords

  • Aspartate–glutamate carrier
  • Autism
  • Autistic disorder
  • Calcium signaling
  • Mitochondria
  • SLC25A12