항박테리아 면역을 조절하는 미토콘드리아 인자들에 대한 유전학적 연구

Abstract

Mitochondria are important subcellular organelles that exert multiple functions in eurkaryotic cells. For the last decade, many studies have shown that mitochondria play key roles in cellular immunity against pathogens. However, immune functions of mitochondria at the organismal level remain incompletely understood. Here, we identified 16 evolutionarily conserved mitochondrial components that affected the immunity of C. elegans against pathogenic bacteria, Pseudomonas aeruginosa (PA14), by performing a large scale genetic screen. Subsequent analyses revealed that the mitochondrial components modulated anti-bacterial immunity through distinct immune pathways. Among the immune-regulatory mitochondrial factors, mitochondrial chaperone HSP-60 was necessary and sufficient for increasing resistance against PA14. We demonstrated that HSP-60 increased the activity of p38 MAP kinase (PMK-1), which boosted the anti-PA14 immunity. In addition, we found that a fraction of HSP-60 localized to the cytosol and cytosolic HSP-60 was sufficient for increasing PA14 resistance. Cytosol-localized HSP-60 physically interacted with and stabilized MAP kinase kinase (SEK-1), which in turn up-regulated p38 MAP kinase signaling and immunity. Altogether, our data showing the HSP-60-dependent transmission of immune-regulatory signals from mitochondria to the cytosol provides fascinating insights into the role of crosstalk between organelles in host defense mechanisms. Furthermore, our study proposes an intriguing possibility that organisms exploit a component of mitochondria, which may have originated from ancient symbiotic bacteria, to protect host animals via monitoring pathogenic bacteria.