Work

Mitochondrial Oxidative Phosphorylation System Dysfunction in Schizophrenia

Year: 2025

Type: review

Abstract: Schizophrenia (SCZ) is a severe, chronic mental disorder of unknown etiology and limited therapeutic options. Bioenergetic deficits in the oxidative phosphorylation system (OXPHOS) during early postnatal brain development may underlie disrupted neuronal metabolism and synaptic signaling, contributing to the neurodevelopmental and behavioral disturbances observed in patients. This narrative review summarizes updated evidence linking mitochondrial-OXPHOS dysfunction to SCZ pathophysiology. The novelty lies in the focus on OXPHOS dysfunction at the enzymatic/functional level, rather than on genetic, transcriptional, or oxidative parameters. While complex I impairment has long been highlighted and proposed as a peripheral marker of the disease, recent studies also report alterations in other OXPHOS complexes and their precursors. These findings suggest that OXPHOS dysfunction is not isolated to a single enzymatic component but affects broader mitochondrial function, alongside oxidative stress, contributing to disease progression through mechanisms involving apoptosis, accelerated aging, and synaptic deterioration. OXPHOS dysfunction in both central and peripheral tissues further supports its relevance to SCZ. Overall, the literature points to mitochondrial OXPHOS abnormalities as a significant biological feature of SCZ. Whether these alterations are causal factors or consequences of disease processes remains unclear. Understanding OXPHOS dysregulation may open new avenues for targeted therapies.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms26094415