FMRP attenuates activity dependent modifications in the mitochondrial proteome

Homeostatic plasticity is necessary for the construction and maintenance of functional neuronal networks, but principal molecular mechanisms required for or modified by homeostatic plasticity are not well understood. We recently reported that homeostatic plasticity induced by activity deprivation is dysregulated in cortical neurons from Fragile X Mental Retardation protein (FMRP) knockout mice (Bulow et al. in Cell Rep 26: 1378-1388 e1373, 2019). These findings led us to hypothesize that identifying proteins sensitive to activity deprivation and/or FMRP expression could reveal pathways required for or modified by homeostatic plasticity. Here, we report an unbiased quantitative mass spectrometry used to quantify steady-state proteome changes following chronic activity deprivation in wild type and Fmr1(-/y) cortical neurons. Proteome hits responsive to both activity deprivation and the Fmr1(-/y) genotype were significantly annotated to mitochondria. We found an increased number of mitochondria annotated proteins whose expression was sensitive to activity deprivation in Fmr1(-/y) cortical neurons as compared to wild type neurons. These findings support a novel role of FMRP in attenuating mitochondrial proteome modifications induced by activity deprivation.

Automated summary

This study found an increased number of mitochondrial annotated proteins in the proteome of cortical neurons sensitive to both activity deprivation and Fmr1(-/y) genotype, suggesting a novel role of FMRP in attenuating mitochondrial proteome modifications induced by activity deprivation.