# Stage-Specific Proteomic Adaptations to Heme-Induced Oxidative Stress in Aedes aegypti: Differential Mechanisms in Larvae and Adults

## TL;DR

This study reveals how Aedes aegypti mosquitoes use different proteomic strategies in larvae and adults to handle heme-induced oxidative stress during blood digestion.

## Contribution

The paper identifies stage-specific proteomic adaptations to heme toxicity in Aedes aegypti larvae and adults.

## Key findings

- Larvae downregulate metabolic and antioxidant proteins but upregulate mitochondrial MnSOD and cytoskeletal proteins.
- Adults show a coordinated bioenergetic response with enriched mitochondrial and redox pathways.
- Both stages exhibit heme-induced structural remodeling via cuticle-associated proteins.

## Abstract

Heme released during blood digestion represents a major oxidative challenge for hematophagous insects, promoting the generation of reactive oxygen species (ROS) and redox imbalance. Although Aedes aegypti has evolved specialized mechanisms to mitigate heme toxicity, how these responses vary across developmental stages remains poorly understood. Here, we applied quantitative proteomics to compare the effects of heme exposure in larvae and adult females. In larvae, heme treatment predominantly led to downregulation of metabolic and antioxidant proteins, consistent with a shift toward energy conservation and growth regulation. Nonetheless, selective upregulation of proteins associated with mitochondrial MnSOD activity, lipid remodeling, and cytoskeletal organization indicates the engagement of complementary protective mechanisms. In contrast, adults exhibited a coordinated bioenergetic response, characterized by enrichment of mitochondrial pathways, redox-related proteins, and molecular chaperones, reflecting enhanced resilience to oxidative stress. Enrichment of cuticle-associated proteins in both stages further suggests heme-induced structural remodeling. Together, these findings demonstrate that A. aegypti employs divergent, stage-specific proteomic strategies to cope with heme toxicity: larvae suppress metabolic activity while maintaining structural and redox homeostasis, whereas adults reinforce mitochondrial function and proteostatic defenses. These insights advance our understanding of mosquito redox biology and highlight stage-specific vulnerabilities that may be exploited for innovative vector control strategies.