Progressive Mitochondrial Dysfunction Impairs Visual Signal Transduction and Induces Retinal Degeneration in Drosophila

Jinguo Cao¹Yining Li¹Xiaohui Hu²Zhaoqi Wu¹Jiting Zhang¹Yue Zhou³Wei Luan³Wen Hu^1,3*Jianhong Tang^1*

• ¹Gannan Medical University, Ganzhou, China
• ²Gannan Health Vocational College, Ganzhou, Jiangxi Province, China
• ³Soochow University, Suzhou, Jiangsu Province, China

Mitochondrial dysfunction is closely associated with the pathogenesis of retinitis pigmentosa (RP), often through the generation of reactive oxygen species (ROS), which disrupt visual signal transduction. However, in certain instances, mitochondrial dysfunction does not correlate with an increase in ROS, and the precise mechanisms by which mitochondrial dysfunction contributes to RP remain poorly understood. In this study, we demonstrate that mitochondrial dysfunction can also impair visual signal transduction through ROS-independent mechanisms. Specifically, we identify that mitochondrial dysfunction affects key processes in photo-transduction, including activation and bleaching, leading to the degrada-tion of photoreceptor proteins and, ultimately, retinal degeneration. This study reveals that mitochondrial dysfunction influences RP through mul-tifaceted pathways, underscoring its role in both hereditary and age-related forms of visual diseases. This study enhances the understanding of the molecular mechanisms underlying RP and establishes a novel model for investigating mitochondrial dysfunction in visual pathologies.