2025/12/07 by Shay Geula, Inna Grosheva, Yehudit Zaltsman +3 · 1 voice
Medicine · Biochemistry, Genetics and Molecular Biology · #Parkinson's Disease Mechanisms and Treatments #Mitochondrial Function and Pathology #Coenzyme Q10 studies and effects
paper · doi:10.64898/2025.12.05.692538
openalex publication_date 2025/12/07 · openalex created_date 2025/12/08 · openalex updated_date 2026/07/14
Abstract α-Synuclein (αSyn) is widely associated with Parkinson’s disease pathology, yet its physiological impact on cellular metabolism remains unclear. Here we show that stable αSyn expression in HEK293 cells induces coordinated metabolic remodeling that enhances mitochondrial resilience. αSyn interacts with lactate dehydrogenase A (LDHA) and αSyn–expressing clones exhibit elevated LDHA activity. Moreover, these clones exhibit increased lactate secretion, enhanced glycolysis, and reduced mitochondrial-reactive oxygen species, coupling metabolic rewiring to improved mitochondrial adaptation. Strikingly, following chronic low-dose rotenone preconditioning, αSyn– expressing clones acquire robust resistance to subsequent respiratory complex I inhibition, revealing a potent αSyn–dependent mitohormetic response. These findings identify αSyn as a conditional metabolic modulator that supports mitochondrial adaptation under sustained stress.