# Mitochondrial remodeling and metabolic reprogramming drive long-term salinity adaptation in Tetrahymena thermophila

## TL;DR

This study explores how the ciliate Tetrahymena thermophila adapts to long-term salt stress through changes in mitochondria and metabolism, offering insights into microbial responses to salinization.

## Contribution

The study reveals novel adaptive strategies in Tetrahymena thermophila involving mitochondrial remodeling and metabolic reprogramming under chronic salt stress.

## Key findings

- Adapted lineages show a trade-off between delayed growth and osmotic resilience.
- Transcriptomic and proteomic analyses highlight upregulated DNA replication and glutathione metabolism.
- Mitochondrial remodeling supports ATP production through ER contacts.

## Abstract

Salinization of inland waters, driven by climate change and human activities, poses a major threat to aquatic ecosystems. While species can swiftly adapt to environmental stress, the molecular mechanisms underpinning this adaptation remain to be fully elucidated. This study seeks to clarify the complex adaptive strategies employed by the freshwater ciliate Tetrahymena thermophila in response to chronic salt stress through the methodologies of experimental evolution and multi-omics integration. The findings indicate that three lineages adapted to salt (ST-4, ST-8, and ST-12), which evolved under a regime of increasing NaCl concentration, demonstrated a trade-off between delayed growth and osmotic resilience. Transcriptomic and proteomic analyses revealed key evolutionary priorities, including (i) the co-upregulation of pathways related to DNA replication, glutathione metabolism, and endoplasmic reticulum (ER) protein processing, (ii) the suppression of lipid catabolism alongside the accumulation of lipid droplets mediated by START2, and (iii) mitochondrial remodeling through the expansion of ER contacts to sustain ATP production. Interestingly, the adaptation to salt appears to tolerate genome instability induced by replication stress through the dysregulation of replisome components, specifically the upregulation of Prim1 and downregulation of LIG, while also evading antioxidant defenses via the compartmentalization of oxidative damage. These results contribute to a framework in which protists effectively balance lipid-mediated osmoregulation, controlled mutagenesis, and organelle metabolism to navigate salinity challenges, thereby offering predictive insights into microbial adaptation thresholds within evolving ecosystems.

Salinization of inland waters is a growing concern due to climate change and human activities. Understanding how organisms adapt to saline environments is vital. Tetrahymena thermophila, a model organism, was studied to explore its adaptation mechanisms. The findings show that through gene regulation, it can acclimate to high salt conditions. The role of mitochondria in metabolic reprogramming during this process is significant. This research contributes to a more profound understanding of how organisms adapt to saline stress and the molecular mechanisms underlying such adaptations, which may aid in predicting and managing the impacts of salinization on aquatic ecosystems.