Role of mitochondrial translation in modulating inflammatory disease outcome: Current knowledge and future perspectives.

Mitochondrial translation is crucial for maintaining cellular respiration, energy balance, calcium signaling, apoptosis, immune surveillance, and the regulation of inflammatory responses. This specialized process, involving mitochondrial rRNAs, tRNAs, mitoribosomes, and nuclear-encoded translation factors, ensures the synthesis of mitochondrially encoded proteins that support oxidative phosphorylation. The mitochondrial translation cycle is tightly regulated by RNA-binding proteins, mitochondrial unfolded protein response, and stress-responsive pathways such as mTOR, particularly during metabolic shifts and immune activation. Emerging evidence highlights mitochondrial translation as a critical modulator of inflammation. In this review, we describe alteration in mitochondrial-specific translation dynamics in immune cells, its adaptation to stress, and its interplay with organelle-wide signaling via mito-nuclear and mito-cytosolic communication. We focus on the alterations in mitochondrial translation machinery, including mitoribosomal proteins, rRNA, tRNA synthetases or other regulatory factors linked to inflammatory diseases, including neurodegeneration, IBD, metabolic and cardiovascular disorders. We further examine how mitochondrial translation influences immune responses through mitochondrial DNA/RNA release, activation of mitochondrial damage-associated molecular patterns, and inflammasomes such as NLRP3. Collectively, mitochondrial translation functions as an immune-centric checkpoint that presents a promising therapeutic target for intervention in inflammation-driven diseases.