Precision autophagy in the kidney: Closed-loop, explainable AI-guided titration of mitophagy in injury and repair

Develop a closed-loop platform integrating super-resolution mitochondria-targeted dyes, ROS reporters, mitophagy reporters (e.g., mito-QC), and explainable AI pipelines for autophagy state classification and tracking in ex vivo kidney organoids and in vivo imaging. Use high-resolution 3D histology and spatial omics to map intervention effects across nephron segments. The AI controller will dynamically titrate autophagy modulators (MTOR inhibitors, TFEB agonists, SIRT3 activators) based on real-time flux and ROS measurements to maintain autophagy within a protective 'Goldilocks zone,' preventing damage from both insufficient and excessive autophagy. This approach aims to establish a new paradigm for precision modulation of cellular recycling in kidney injury and repair.

References:

1. Autophagy and mitophagy: physiological implications in kidney inflammation and diseases.. D. Bhatia, Mary E. Choi (2023). AJP - Renal Physiology.
2. Artificial targeting of autophagy components to mitochondria reveals both conventional and unconventional mitophagy pathways. Katharina C Lorentzen, Alan R Prescott, I. Ganley (2024). Autophagy.
3. Advances in SIRT3 involvement in regulating autophagy-related mechanisms. Shuangyun Xi, Weijun Chen, Yong Ke (2024). Cell Division.
4. Explainable AI to unveil cellular autophagy dynamics. Oriana Presacan, María Hernández Mesa, A. C. Aldea, Siri Andresen, Amani Al Outa, Julie Aarmo Johannessen, Bogdan Ionescu, Helene Knævelsrud, M. A. Riegler (2025). PLoS ONE.
5. A Mitochondria-Targeted Dye for Investigating Mo Mineral Powder Induced Cytotoxicity through SIM Super-Resolution Imaging.. Lai Wang, Zhiqi Su, Daqing Ma, Yanlin Qin, Yi Xiao, Xinfu Zhang (2025). ACS Applied Materials and Interfaces.
6. From morphology to single-cell molecules: high-resolution 3D histology in biomedicine. Xintian Xu, Jimeng Su, Rongyi Zhu, Kailong Li, Xiaolu Zhao, Jibiao Fan, Fengbiao Mao (2025). Molecular Cancer.
7. SINGLE-CELL AND SPATIAL OMICS FOR MAPPING CELLULAR SENESCENCE IN HEALTH, AGING AND DISEASE. Rong Fan (2023). Innovation in aging.