Mitochondrial Bioenergetics in Acute Tubular Injury: Metabolic Plasticity, Cell Fate, and Translational Opportunities

Acute tubular injury (ATI), often called acute tubular necrosis in clinical practice, is a major tissue-injury pattern in acute kidney injury (AKI), although necrosis is variable. Tubular transport places a high demand on mitochondrial ATP production. Ischemia-reperfusion, sepsis, and nephrotoxins disrupt this supply through respiratory dysfunction, calcium and redox imbalance, and mitochondrial DNA stress. The consequences depend on the nephron segment, cause of injury, and timing. This narrative review uses those differences to connect mitochondrial quality control and metabolic adaptation with cell fate, biomarkers, and therapeutic opportunities. We distinguish changes in gene expression or metabolite abundance from measured pathway function, and experimentally supported mechanisms from human associations and clinical intervention results. Human renal physiology, tissue studies, organ-perfusion experiments, and small randomized trials provide useful translational evidence. However, an increase in circulating NAD+ or an encouraging biomarker signal does not establish improved kidney outcomes. The proposed phase-based framework is therefore a guide to testing mechanisms and treatment windows, not a universal sequence from early adaptation to late harm. Clinical translation requires evidence that an intervention reaches its renal target, acts within a relevant window, and benefits patients beyond current supportive care.