Box C/D small nucleolar ribonucleoproteins regulate mitochondrial surveillance and innate immunity

Monitoring mitochondrial function is crucial for organismal survival. This task is performed by mitochondrial surveillance or quality control pathways, which are activated by signals originating from mitochondria and relayed to the nucleus (retrograde response) to start transcription of protective genes. In Caenorhabditis elegans, several systems are known to play this role, including the UPRmt, MAPK(mt), and the ESRE pathways. These pathways are highly conserved and their loss compromises survival following mitochondrial stress. In this study, we found a novel interaction between the box C/D snoRNA core proteins (snoRNPs) and mitochondrial surveillance and innate immune pathways. We showed that box C/D, but not box H/ACA, snoRNPs are required for the full function of UPRmt and ESRE upon stress. The loss of box C/D snoRNPs reduced mitochondrial mass, mitochondrial membrane potential, and oxygen consumption rate, indicating overall degradation of mitochondrial function. Concomitantly, the loss of C/D snoRNPs increased immune response and reduced host intestinal colonization by infectious bacteria, improving host resistance to pathogenesis. Our data may indicate a model wherein box C/D snoRNP machinery regulates a "switch" of the cell's activity between mitochondrial surveillance and innate immune activation. Understanding this mechanism is likely to be important for understanding multifactorial processes, including responses to infection and aging. Author summaryMitochondrial health is important for organismal survival. Multiple cellular pathways are dedicated to actively monitoring mitochondrial status, termed as the mitochondrial surveillance system, to provide better defense towards variety of stresses. These systems are highly conserved and present in both C. elegans and humans. Here we report that the Box C/D snoRNA core proteins (snoRNPs), normally associated with modification of ribosomal RNA, play a role in mitochondrial surveillance and innate immune pathways. The loss of this protein complex reduced mitochondrial surveillance pathway activation after stress but increased immune responses. As mitochondrial surveillance, innate immunity, and box C/D snoRNP pathways are conserved in humans, understanding their roles in modulating cell biology during mitochondrial crises is essential for mitigating stress and restoring health after damage.