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This study reveals that the mitochondrial unfolded protein response (UPRMT) in C. elegans is activated by E. faecalis infection through nutrient competition and oxidative stress rather than direct bacterial toxins. Because both organisms cannot produce heme independently, E. faecalis infection causes severe heme deficiency in the host, disrupting mitochondrial function and triggering the UPRMT. This mitochondrial stress is intensified by oxidative damage from hydrogen peroxide produced by the host's own immune system, repositioning the UPRMT as a metabolic and oxidative stress sensor during infection.
Why it matters
This research challenges the conventional understanding that pathogen-induced mitochondrial stress responses require specialized bacterial toxins, suggesting instead that nutrient competition between host and pathogen can be a primary trigger. These findings may inform new therapeutic approaches targeting metabolic vulnerabilities in host-pathogen interactions and expand our understanding of how nutrient immunity functions at the cellular level.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Mitochondria serve as critical signaling hubs that monitor the intracellular environment to orchestrate cellular stress responses during pathogen infection. The mitochondrial unfolded protein response (UPRMT), a key surveillance pathway, is widely considered to be activated by pathogen-derived toxins that directly damage host mitochondria. In contrast to this prevailing model, we demonstrate that E. faecalis, which lacks specialized mitochondrial toxins, activates the UPRMT in C. elegans via a combination of metabolic and oxidative stress. As both C. elegans and E. faecalis are heme auxotrophs, E. faecalis-ingested animals result in severe heme deficiency, leading to the disruption of the electron transport chain and activation of the UPRMT. During live infection, this primary mitochondrial stress is further amplified due to the Fenton reaction, driven by host NADPH oxidase BLI-3-generated hydrogen peroxide. Ultimately, our findings position the UPRMT as a fundamental homeostatic sensor that monitors metabolic and oxidative imbalances at the host-pathogen interface.
Source: The UPRMT is a critical mediator of nutrient immunity