Modulating inter-mitochondrial contacts to increase membrane potential for mitigating blue light damage

Wang, Y., Qiu, K., Zou, W., Amom, P., Ganjawala, T., Lee, E., Tian, Z., Xu, X., Huang, T., Tsai, N.-P., Shi, D., Kang, P., Bai, H., Zacharias, A. L., Zhang, K., Diao, J.

University of Cincinnati College of MedicineUniversity of Cincinnati College of Medicine · biorxiv

Paper

Abstract

Mitochondrial membrane potential (MMP) is essential for mitochondrial functions, yet current methods for modulating MMP lack precise spatial and temporal control. Here, we present an optogenetic system that enables reversible formation of inter-mitochondrial contacts (mito-contacts) with high spatiotemporal precision. Blue light stimulation induces rapid formation of mito-contacts, which fully dissipate upon cessation of illumination. These light-induced mito-contacts can enhance MMP, leading to increased ATP production under stress conditions. Moreover, in human retinal cells and C. elegans, high MMP induced by mito-contacts alleviates the deleterious effects of prolonged blue light exposure, restoring energy metabolism and extending organismal lifespan. This optogenetic approach provides a powerful tool for modulating MMP and offers potential therapeutic applications for diseases linked to mitochondrial dysfunction.

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Research summary

The paper claims that optogenetic modulation of inter-mitochondrial contacts can enhance mitochondrial membrane potential and extend lifespan in model organisms. This research addresses mitochondrial dysfunction, which is a significant contributor to aging and age-related diseases, thus providing insights into potential longevity interventions.

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