Abraham, T. | Search bioRxiv

bioRxiv2025

Algae-specific Immune Modulation Influences Responses to Heat and Pathogen Challenge in a Symbiotic Coral

The role of symbiotic algae in coral life history and host health is well documented, but the immune and physiological trade-offs of hosting these symbionts remain less explored. While association with the algal symbionts of the genus Durusdinium is known to confer thermotolerance, it has also been linked to coral tissue loss under stress. We investigated whether algal type influences host immunity and stress responses in the tropical coral Pocillopora acuta. Durusdinium-hosting (D-hosting) P. acuta have distinct transcriptomic profiles, higher immune-related gene expression, and elevated baseline levels of immunity transcription factor NF-{kappa}B as compared to corals hosting Cladocopium (C-hosting). Under heat challenge, D-hosting P. acuta exhibited tissue loss, oxidative stress, immune and microbial dysregulation, whereas C-hosting P. acuta were more susceptible to bleaching, metabolic dysregulation, and decline in nitrogen-fixing and antioxidant-producing bacteria. Finally, infection with the the bacterium Vibrio coralliilyticus caused high tissue loss in D-hosting corals, but not in C-hosting corals. Our results suggest a mechanism for how Durusdinium association enhances thermotolerance yet predisposes corals to tissue damage under stress, suggesting immune trade-offs that can compromise host survival under multiple stressors.

genomics↗

bioRxiv2019

Context-dependent activation of SIRT3 is necessary for anchorage-independent survival and metastasis of ovarian cancer cells.

Cells must alter their antioxidant capacity for maximal metastatic potential. However, the antioxidant adaptations required for transcoelomic metastasis, which is the passive dissemination of cancer cells in the peritoneal cavity as seen in ovarian cancer, have largely remained unexplored. Contradicting the need for oxidant scavenging by tumor cells is the observation that expression of the nutrient stress sensor and regulator of mitochondrial antioxidant defenses, SIRT3, is suppressed in many primary tumors. We discovered that this mitochondrial deacetylase is however, upregulated in a context-dependent manner in cancer cells. SIRT3 activity and expression transiently increased following ovarian cancer cell detachment and in tumor cells derived from malignant ascites of high-grade serous adenocarcinoma patients. Mechanistically, SIRT3 prevents mitochondrial superoxide surges in detached cells by regulating the manganese superoxide dismutase SOD2. This mitochondrial stress response is under dual regulation by SIRT3. SIRT3 rapidly increases SOD2 activity as an early adaptation to cellular detachment, which is followed by SIRT3-dependent transcriptional increases in SOD2 during sustained anchorage-independence. In addition, SIRT3 inhibits glycolytic capacity in anchorage-independent cells thereby contributing to metabolic changes in response to detachment. While manipulation of SIRT3 expression has few deleterious effects on cancer cells in attached conditions, SIRT3 up-regulation and SIRT3-mediated oxidant scavenging following matrix detachment are required for anoikis resistance in vitro, and both SIRT3 and SOD2 are necessary for colonization of the peritoneal cavity in vivo. Our results highlight the novel context-specific, pro-metastatic role of SIRT3 in ovarian cancer.

cancer biology↗