MitoCARB: Exploring the role of reactive carbonyls and glyoxalase system in metabolic stress responses of marine bivalves from extreme habitats

• Applicant: Professorin Dr. Inna M. Sokolova
• Subject Area: Animal Physiology and Biochemistry
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 575179366

Metabolism is essential for all living organisms, driving energy production and the synthesis of biomolecules necessary for life. Marine bivalves, such as mussels and oysters, display remarkable metabolic flexibility that enables them to survive the extreme environmental fluctuations of intertidal zones. These habitats are characterized by rapid changes in temperature, oxygen availability, and salinity, posing significant physiological challenges. Bivalves cope with these stresses through strategies such as metabolic rate depression and by switching between aerobic and anaerobic pathways. Coordinating these pathways is critical for stress tolerance, yet the underlying mechanisms remain poorly understood. Reactive carbonyl species (RCS), particularly methylglyoxal (MG), are natural byproducts of glycolysis with a dual role as signaling molecules and damaging agents. This duality places MG at the center of aerobic–anaerobic crosstalk, potentially influencing adaptive and maladaptive stress responses. Mitochondria, central to energy metabolism, also play a key role in stress adaptation by fine-tuning metabolic processes to optimize energy production and limit damage under stress. However, the role of RCS in regulating these mitochondrial functions in marine organisms remains unexplored. This project will investigate the role of MG in regulating metabolic function and stress tolerance in intertidal bivalves, focusing on its effects on mitochondrial function and protein stability during environmental stress and aerobic–anaerobic transitions. We hypothesize that low MG concentrations enhance stress tolerance via hormesis-like mechanisms—improving mitochondrial function (mitohormesis), boosting detoxification, and reinforcing protein quality control—whereas high MG levels trigger protein glycation, mitochondrial dysfunction, energy imbalance, AGE accumulation, and inflammation. To test this, mussels and oysters will be exposed to realistic stress scenarios: short-term tidal-like fluctuations and prolonged hypoxia or heat stress. Using integrated biochemical, proteomic, metabolomic, and molecular approaches, we will assess how these conditions affect glycolytic flux, MG metabolism, and proteome stability across tissues, revealing links between MG accumulation, detoxification capacity, and protein damage. We will then manipulate MG levels experimentally to evaluate impacts on mitochondrial function, protein integrity, and cellular homeostasis. Finally, targeted transcript analysis will determine how MG—stress-induced or experimentally altered—modulates protective pathways (antioxidants, glyoxalases, mitochondrial and protein quality control) and stress responses such as apoptosis and inflammation. By uncovering novel mechanisms of metabolic adaptation, this research will enhance our understanding of stress tolerance and metabolic flexibility in marine bivalves, with broader implications for evolutionary biology and environmental stress research.

• DFG Programme: Research Grants