Organelle Crosstalk in Renal Cells: Insights from Cell Biology and Implications for AKI-to-CKD Transition.

The kidney is a highly specialized organ that maintains systemic homeostasis through tightly coordinated cellular and molecular mechanisms. Renal parenchymal cells regulate metabolic waste excretion, electrolyte and acid-base balance, and blood pressure control-functions that rely on the dynamic integration of intracellular organelles. Recent advances in molecular and biochemical research have highlighted how inter-organelle communication is essential for preserving renal cell function and adaptive responses to stress. This review focuses on the molecular crosstalk among key organelles-including the nucleus, endoplasmic reticulum (ER), Golgi apparatus, mitochondria, lysosomes, and peroxisomes-primarily in tubular epithelial cells. We discuss how these interactions coordinate metabolic signaling, protein homeostasis, redox balance, and energy production and how their disruption contributes to maladaptive pathways during acute kidney injury (AKI), ultimately promoting chronic kidney disease (CKD) transition. Particular focus is placed on emerging pathways linking organelle dysfunction to inflammation, fibrosis, and metabolic reprogramming. Furthermore, we highlight recent advances in genetics and molecular therapeutics targeting organelle communication, including modulation of ER stress responses, mitochondrial biogenesis, and lysosomal function. Clinically approved agents, such as mTOR inhibitors, and experimental approaches-such as chemical chaperones and mitochondrial transplantation-demonstrate the potential to restore organelle homeostasis and mitigate renal injury. Overall, elucidating the molecular networks governing organelle crosstalk provides critical insights into kidney disease pathogenesis and identifies novel targets for therapeutic intervention in AKI-to-CKD transition.