CSDE1 Associates with TOM20 and Mitochondrial Protein-Encoding mRNAs in Sensory Neurons

Abstract

Mitochondrial proteostasis in neurons relies on the coordinated expression, targeting, and import of a predominantly nuclear-encoded proteome to meet high metabolic demands. Here, we identify the RNA-binding protein cold shock domain containing E1 (CSDE1) as a TOM20-associated factor linked to mitochondrial protein-encoding mRNAs in sensory neurons. CSDE1 immunoprecipitation followed by sequencing from na & iuml;ve dorsal root ganglion tissue revealed association with nuclear-encoded mitochondrial mRNAs enriched for inner membrane/matrix and oxidative phosphorylation pathways. A subset of CSDE1 localized to mitochondria and associated with the outer mitochondrial membrane import receptor TOM20 via its N-terminal region in an RNA-independent manner. In cultured sensory neurons, CSDE1 depletion reduced the mitochondrial-fraction abundance of representative nuclear-encoded electron transport chain mRNAs and decreased the abundance of selected mitochondrial proteins in the mitochondrial fraction. CSDE1 depletion reduced TMRM-positive mitochondrial puncta density along sensory neurites, without significantly increasing MitoSOX-detectable mitochondrial superoxide signals under either basal or oxidative challenge conditions. These findings identify CSDE1 as a TOM20-associated RNA-binding protein linked to mitochondrial protein-encoding transcripts in sensory neurons and support a model in which CSDE1 contributes to mitochondria-associated post-transcriptional regulation.