Mitochondrial dynamics and function in neural differentiation: a systematic review

Area of Science:

• Neuroscience
• Cell Biology
• Developmental Biology

Background:

• Mitochondrial function is vital for neural differentiation, but its dynamic roles are not fully understood.
• This review synthesizes evidence on mitochondria in neural stem cell differentiation and neurodevelopmental disorders.

Purpose of the Study:

• To systematically review and synthesize current evidence on mitochondrial contributions to neural stem cell differentiation.
• To explore the temporal dynamics and molecular mechanisms of mitochondrial regulation during neural differentiation.
• To investigate the implications of mitochondrial dysfunction in neurodevelopmental disorders.

Main Methods:

• Systematic literature search of PubMed, Web of Science, and Scopus databases up to January 2025.
• Inclusion of studies on mitochondrial properties during neural differentiation.
• Data extraction on temporal changes, molecular mechanisms, and pathological links, with quality assessment.

Main Results:

• Fifty studies revealed stage-specific mitochondrial regulation: fragmentation/ROS in early stages, fusion/oxidative phosphorylation in intermediate, and mature networks in late stages.
• Key molecular mechanisms involved calcium signaling, Wnt/β-catenin pathway, and fusion/fission protein dynamics.
• Mitochondrial dysfunction was linked to impaired neural differentiation in various neurodevelopmental disorders.

Conclusions:

• Neural differentiation involves stage-specific mitochondrial changes in morphology, metabolism, and signaling.
• Identified molecular pathways offer therapeutic targets for neurodevelopmental disorders.
• Future research should standardize methods, explore tissue-specific regulation, and develop targeted interventions for regenerative medicine.