Link between the mechanism of mitophagy and schizophrenia: A narrative review

Despite extensive research, the precise pathophysiology underlying schizophrenia remains unclear, but accumulating evidence suggests that mitochondrial dysfunction and oxidative stress play significant roles in its development. Mitophagy, the selective degradation of damaged or dysfunctional mitochondria, plays a critical role in maintaining cellular homeostasis and is increasingly recognized for its implications in various neuropsychiatric disorders, including schizophrenia. This review examines current knowledge regarding mitophagy and its association with schizophrenia. The literature was searched in PubMed- Medline and Scopus databases, and as a narrative review, the methodology focuses on the comprehensive coverage and synthesis of relevant studies. The hypothesis of the review claims that there is a link between mitophagy and schizophrenia. The terms used in the search query are "mitophagy", "schizophrenia" with the Boolean variable "AND". The relationship between mitophagy and schizophrenia is complex and multifaceted, involving mitochondrial dysfunction, neuroinflammation, and the integrity of oligodendrocytes and microglia. Schizophrenia is associated with dysfunctional mitophagy and elevated oxidative stress. These mechanisms may help to explain overlapping symptoms, particularly cognitive deficits. While the emerging data linking mitophagy and schizophrenia are promising, current research has limitations. Much of the evidence for mitophagy dysfunction in schizophrenia comes from animal models or postmortem studies, which may not fully capture the complexity of the disorder in humans. Moreover, mitophagy is challenging to study in vivo, particularly in the human brain, making it difficult to directly observe mitophagy processes in patients with schizophrenia. Mitophagy and its dysfunction may contribute to the pathophysiology of schizophrenia. Evidence suggests that impaired mitophagy can lead to energy dysregulation, oxidative stress, and neuroinflammation, all of which are implicated in schizophrenia. While more research is needed, the potential link between mitophagy and schizophrenia presents an interesting area for future studies and therapeutic development. Targeting mitophagy could offer new approaches for addressing cognitive and negative symptoms, providing hope for improved treatment outcomes.