LARP-1 maintains the structure and function of mitochondria by regulating mitochondrial crista-related proteins

Mitochondria are the metabolic center and powerhouses of cells by coordinating the tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS) and electron transport to generate ATP, which provide energy for cell survival and functional maintenance. This is attributed to the key structure of mitochondria cristae, which are formed by the inward folding of inner mitochondrial membranes. Numerous studies have demonstrated that RNA-binding proteins play an important role in maintaining the normal structure and function of mitochondria. However, the relevant mechanism remains unclear. Here, we report that the RNA-binding protein LARP-1 affects the structure and function of mitochondria by disrupting crista-related proteins, including the MICOS complex, respiratory chain complexes, and the proton-transporting ATP synthase complex. Using APEX-based proximity labeling assays, we pulled down mRNAs associated with LARP-1::APEX2, and determined the identities of mRNAs by sequencing. Among the 653 LARP-1::APEX2-enriched mRNAs, 37.5% (245/653) encode mitochondrial proteins, of which 71.8% (176/245) were identified to be down-regulated in larp-1 mutants by LC-MS analysis of purified mitochondria. In addition, mRNAs encoding components of the MICOS complex, respiratory chain complexes, and ATP synthase complex were strongly enriched, suggesting that they were associated with LARP-1. RNA-seq of immunoprecipitation results of fusion proteins LARP-1::GFP (knock in) or LARP-1::APEX2 (knock in).