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• W3178347495 abstract "Eukaryotic cells maintain proteostasis through mechanisms that require cytoplasmic and mitochondrial translation. Genetic defects affecting cytoplasmic translation perturb synapse development, neurotransmission, and are causative of neurodevelopmental disorders, such as Fragile X syndrome. In contrast, there is little indication that mitochondrial proteostasis, either in the form of mitochondrial protein translation and/or degradation, is required for synapse development and function. Here we focus on two genes deleted in a recurrent copy number variation causing neurodevelopmental disorders, the 22q11.2 microdeletion syndrome. We demonstrate that SLC25A1 and MRPL40, two genes present in the microdeleted segment and whose products localize to mitochondria, interact and are necessary for mitochondrial ribosomal integrity and proteostasis. Our <i>Drosophila</i> studies show that mitochondrial ribosome function is necessary for synapse neurodevelopment, function, and behavior. We propose that mitochondrial proteostasis perturbations, either by genetic or environmental factors, are a pathogenic mechanism for neurodevelopmental disorders. <b>SIGNIFICANCE STATEMENT</b> The balance between cytoplasmic protein synthesis and degradation, or cytoplasmic proteostasis, is required for normal synapse function and neurodevelopment. Cytoplasmic and mitochondrial ribosomes are necessary for two compartmentalized, yet interdependent, forms of proteostasis. Proteostasis dependent on cytoplasmic ribosomes is a well-established target of genetic defects that cause neurodevelopmental disorders, such as autism. Here we show that the mitochondrial ribosome is a neurodevelopmentally regulated organelle whose function is required for synapse development and function. We propose that defective mitochondrial proteostasis is a mechanism with the potential to contribute to neurodevelopmental disease." @default.
• W3178347495 created "2021-07-19" @default.
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• W3178347495 date "2021-07-14" @default.
• W3178347495 modified "2023-10-09" @default.
• W3178347495 title "Mitochondrial Proteostasis Requires Genes Encoded in a Neurodevelopmental Syndrome Locus" @default.
• W3178347495 cites W1516294781 @default.
• W3178347495 cites W1541267199 @default.
• W3178347495 cites W1553155385 @default.
• W3178347495 cites W1566509230 @default.
• W3178347495 cites W1613369435 @default.
• W3178347495 cites W1830339052 @default.
• W3178347495 cites W1895007034 @default.
• W3178347495 cites W1934152683 @default.
• W3178347495 cites W1944444102 @default.
• W3178347495 cites W1959897390 @default.
• W3178347495 cites W1976555450 @default.
• W3178347495 cites W1983660707 @default.
• W3178347495 cites W1985213868 @default.
• W3178347495 cites W1987702513 @default.
• W3178347495 cites W1988011192 @default.
• W3178347495 cites W1989747504 @default.
• W3178347495 cites W1994640446 @default.
• W3178347495 cites W2002141156 @default.
• W3178347495 cites W2006805865 @default.
• W3178347495 cites W2009401980 @default.
• W3178347495 cites W2011813312 @default.
• W3178347495 cites W2015832139 @default.
• W3178347495 cites W2016104434 @default.
• W3178347495 cites W2021743398 @default.
• W3178347495 cites W2028386886 @default.
• W3178347495 cites W2032022203 @default.
• W3178347495 cites W2038481472 @default.
• W3178347495 cites W2054091111 @default.
• W3178347495 cites W2054855377 @default.
• W3178347495 cites W2055655674 @default.
• W3178347495 cites W2056213320 @default.
• W3178347495 cites W2056589536 @default.
• W3178347495 cites W2058428720 @default.
• W3178347495 cites W2059148325 @default.
• W3178347495 cites W2059613997 @default.
• W3178347495 cites W2063130661 @default.
• W3178347495 cites W2066650294 @default.
• W3178347495 cites W2069775190 @default.
• W3178347495 cites W2072652550 @default.
• W3178347495 cites W2073109785 @default.
• W3178347495 cites W2074261331 @default.
• W3178347495 cites W2079030640 @default.
• W3178347495 cites W2084352245 @default.
• W3178347495 cites W2086020590 @default.
• W3178347495 cites W2087519253 @default.
• W3178347495 cites W2103592460 @default.
• W3178347495 cites W2110373490 @default.
• W3178347495 cites W2112572641 @default.
• W3178347495 cites W2118122718 @default.
• W3178347495 cites W2119706891 @default.
• W3178347495 cites W2120095635 @default.
• W3178347495 cites W2122380998 @default.
• W3178347495 cites W2129390057 @default.
• W3178347495 cites W2133961780 @default.
• W3178347495 cites W2136608375 @default.
• W3178347495 cites W2137076924 @default.
• W3178347495 cites W2137220579 @default.
• W3178347495 cites W2144575277 @default.
• W3178347495 cites W2147140183 @default.
• W3178347495 cites W2148043260 @default.
• W3178347495 cites W2150790075 @default.
• W3178347495 cites W2151979231 @default.
• W3178347495 cites W2155648855 @default.
• W3178347495 cites W2159675211 @default.
• W3178347495 cites W2160107586 @default.
• W3178347495 cites W2163302580 @default.
• W3178347495 cites W2169589032 @default.
• W3178347495 cites W2170971711 @default.
• W3178347495 cites W2207498068 @default.
• W3178347495 cites W2253685848 @default.
• W3178347495 cites W2268456576 @default.
• W3178347495 cites W2289876562 @default.
• W3178347495 cites W2312266417 @default.

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