Non-Mammalian Models for Mitochondria Research in CNS Disorders

Mitochondrial dysfunction is increasingly recognized as a major contributor to central nervous system (CNS) disorders, including neurodegenerative and neuropsychiatric diseases. Animal models are essential for elucidating disease mechanisms and supporting the development of new therapeutic strategies. Among these models, non-mammalian organisms offer distinct advantages, including low cost, rapid life cycles, genetic tractability, and suitability for large-scale, high-throughput studies. Organisms such as Saccharomyces cerevisiae, Dictyostelium discoideum, Caenorhabditis elegans, Drosophila melanogaster, and Danio rerio have substantially advanced the understanding of mitochondrial processes relevant to CNS pathology. Studies using these models have revealed conserved mechanisms involving mitophagy, mitochondrial quality control, respiratory function, bioenergetic signaling, and neurodegenerative pathways. Their strengths, including scalability, live imaging capacity, and efficient genetic manipulation, have accelerated disease modeling and therapeutic discovery. However, simplified physiology, evolutionary distance from humans, and the incomplete representation of complex CNS organization limit their translational relevance and often require validation in higher-order organisms. Nevertheless, integrating these models into CNS research, particularly alongside emerging technologies, provides a powerful strategy for linking fundamental mitochondrial biology with translational neuroscience. This review summarizes the use of non-mammalian models in neuroscience research, with an emphasis on mitochondrial dysfunction in CNS disorders and their potential to support future therapeutic advances.