Mitochondrial metabolism and targeted treatment strategies in ischemic-induced acute kidney injury (AKI) are critical areas of research due to the high morbidity and mortality associated with AKI. Ischemia-reperfusion injury (IRI) is a major cause of AKI, particularly in conditions like hypotension, sepsis, and surgical procedures. Mitochondria, central to energy production, play a key role in the early stages of IRI, contributing to ROS production, inflammation, and apoptosis. Mitochondrial dysfunction in renal tubular epithelial cells (TECs) leads to cell death and worsens AKI. Recent studies highlight the importance of mitochondrial pathology in IRI-AKI and the potential of targeting mitochondrial dysfunction for therapeutic intervention. Mitochondrial dysfunction is linked to energy metabolism disorders and is a potential mechanism underlying AKI. Loss of transcription factor A (TFAM) due to mitochondrial ROS (mtROS) causes mitochondrial dysfunction in TECs. Mitophagy, a process that removes damaged mitochondria, protects TECs during AKI. Future research should focus on screening effective interventions to regulate mitochondrial metabolism. Key therapeutic targets include mitophagy, mitochondrial energy metabolism, and ROS regulation. Mitophagy, mediated by the PINK1-PARK2 pathway and BNIP3, helps eliminate damaged mitochondria and reduce ROS levels, thereby protecting against AKI. Targeting mitochondrial energy metabolism, such as through PPARα-regulated fatty acid oxidation (FAO), can improve renal function. Sirt5 regulates FAO in TECs, reducing oxygen demand and oxidative stress, thus improving renal function. ROS production is a major contributor to mitochondrial damage and AKI. Mitochondrial antioxidants like MitoQ and BI1 can reduce ROS levels and protect against IRI. Mitochondrial fusion and fission are critical for maintaining mitochondrial function, and dysregulation of these processes contributes to AKI. Therapeutic strategies targeting these processes, such as using Mdivi-1 to inhibit mitochondrial fission, can improve kidney function. Mitochondrial-related biomarkers, such as urinary ATP synthase subunit b (ATPSb) and mitochondrial DNA (mtDNA), show promise for diagnosing and monitoring IRI-AKI. These biomarkers can provide early detection of mitochondrial dysfunction and guide treatment. In conclusion, targeting mitochondrial metabolism, mitophagy, and ROS production offers promising therapeutic strategies for IRI-AKI. Further research is needed to develop effective treatments and validate these approaches in clinical settings.Mitochondrial metabolism and targeted treatment strategies in ischemic-induced acute kidney injury (AKI) are critical areas of research due to the high morbidity and mortality associated with AKI. Ischemia-reperfusion injury (IRI) is a major cause of AKI, particularly in conditions like hypotension, sepsis, and surgical procedures. Mitochondria, central to energy production, play a key role in the early stages of IRI, contributing to ROS production, inflammation, and apoptosis. Mitochondrial dysfunction in renal tubular epithelial cells (TECs) leads to cell death and worsens AKI. Recent studies highlight the importance of mitochondrial pathology in IRI-AKI and the potential of targeting mitochondrial dysfunction for therapeutic intervention. Mitochondrial dysfunction is linked to energy metabolism disorders and is a potential mechanism underlying AKI. Loss of transcription factor A (TFAM) due to mitochondrial ROS (mtROS) causes mitochondrial dysfunction in TECs. Mitophagy, a process that removes damaged mitochondria, protects TECs during AKI. Future research should focus on screening effective interventions to regulate mitochondrial metabolism. Key therapeutic targets include mitophagy, mitochondrial energy metabolism, and ROS regulation. Mitophagy, mediated by the PINK1-PARK2 pathway and BNIP3, helps eliminate damaged mitochondria and reduce ROS levels, thereby protecting against AKI. Targeting mitochondrial energy metabolism, such as through PPARα-regulated fatty acid oxidation (FAO), can improve renal function. Sirt5 regulates FAO in TECs, reducing oxygen demand and oxidative stress, thus improving renal function. ROS production is a major contributor to mitochondrial damage and AKI. Mitochondrial antioxidants like MitoQ and BI1 can reduce ROS levels and protect against IRI. Mitochondrial fusion and fission are critical for maintaining mitochondrial function, and dysregulation of these processes contributes to AKI. Therapeutic strategies targeting these processes, such as using Mdivi-1 to inhibit mitochondrial fission, can improve kidney function. Mitochondrial-related biomarkers, such as urinary ATP synthase subunit b (ATPSb) and mitochondrial DNA (mtDNA), show promise for diagnosing and monitoring IRI-AKI. These biomarkers can provide early detection of mitochondrial dysfunction and guide treatment. In conclusion, targeting mitochondrial metabolism, mitophagy, and ROS production offers promising therapeutic strategies for IRI-AKI. Further research is needed to develop effective treatments and validate these approaches in clinical settings.