The kidney requires a large number of mitochondria to remove waste from the blood and regulate fluid and electrolyte balance. Mitochondria provide the energy to drive these functions and can adapt to different metabolic conditions through pathways like mTOR and AMPK, which activate PGC1α to maintain mitochondrial homeostasis. Mitochondrial dysfunction reduces ATP production, disrupts cellular functions, and leads to renal failure. It plays a role in early stages and progression of diseases like AKI and diabetic nephropathy. Improving mitochondrial homeostasis can restore renal function, and compounds that stimulate mitochondrial biogenesis can help in mouse models of these diseases. Inhibiting DRP1, a fission protein, may reduce ischaemic renal injury. The kidney is one of the most energy-demanding organs. It has a high resting metabolic rate and mitochondrial content. Mitochondria provide energy for ion gradients, essential for reabsorption of glucose, ions, and nutrients. The proximal tubule, which reabsorbs 80% of filtrate, contains the most mitochondria. Mitochondria sense nutrient availability and energy demand, maintaining homeostasis. In this review, the processes involved in maintaining mitochondrial homeostasis and their role in supporting renal function are discussed. The review also explores how diseases like AKI and diabetic nephropathy alter mitochondrial function and how mitochondrial energetics can be targeted for treatment. Mitochondria produce ATP through aerobic respiration, involving the electron transport chain and oxidative phosphorylation. Proximal tubules rely on oxidative phosphorylation for ATP production, while glomerular cells use aerobic and anaerobic respiration. Anaerobic respiration produces ATP but is less efficient. Proximal tubules use fatty acids via β-oxidation for maximal ATP production. Fatty acid metabolism in diseases like AKI and diabetic nephropathy can impair ATP production and mitochondrial function. Antioxidant defenses, including SOD2, catalase, and glutathione, protect mitochondria from ROS. Uncoupling proteins like UCP2 reduce ROS production. Hypoxia activates HIF1α, altering ETC efficiency. Nutrient-sensing pathways like mTOR and AMPK regulate mitochondrial biogenesis. mTORC1 activates PGC1α, while AMPK stimulates mitochondrial biogenesis and energy production. AMPK also inhibits mTORC1 under nutrient deprivation. Mitochondrial homeostasis requires balance between biogenesis, fission, fusion, and mitophagy. PGC1α regulates mitochondrial biogenesis and function. SIRT1 and SIRT3 deacetylate proteins involved in mitochondrial processes. cAMP and cGMP pathways also regulate mitochondrial biogenesis. Mitochondrial dynamics involve fission and fusion, with mitophagy removing damaged mitochondria. PINK1-PARKIN pathway tags mitochondria for degradation. Mitochondrial dysfunction in diseases like AKI and diabetic nephropathy disruptsThe kidney requires a large number of mitochondria to remove waste from the blood and regulate fluid and electrolyte balance. Mitochondria provide the energy to drive these functions and can adapt to different metabolic conditions through pathways like mTOR and AMPK, which activate PGC1α to maintain mitochondrial homeostasis. Mitochondrial dysfunction reduces ATP production, disrupts cellular functions, and leads to renal failure. It plays a role in early stages and progression of diseases like AKI and diabetic nephropathy. Improving mitochondrial homeostasis can restore renal function, and compounds that stimulate mitochondrial biogenesis can help in mouse models of these diseases. Inhibiting DRP1, a fission protein, may reduce ischaemic renal injury. The kidney is one of the most energy-demanding organs. It has a high resting metabolic rate and mitochondrial content. Mitochondria provide energy for ion gradients, essential for reabsorption of glucose, ions, and nutrients. The proximal tubule, which reabsorbs 80% of filtrate, contains the most mitochondria. Mitochondria sense nutrient availability and energy demand, maintaining homeostasis. In this review, the processes involved in maintaining mitochondrial homeostasis and their role in supporting renal function are discussed. The review also explores how diseases like AKI and diabetic nephropathy alter mitochondrial function and how mitochondrial energetics can be targeted for treatment. Mitochondria produce ATP through aerobic respiration, involving the electron transport chain and oxidative phosphorylation. Proximal tubules rely on oxidative phosphorylation for ATP production, while glomerular cells use aerobic and anaerobic respiration. Anaerobic respiration produces ATP but is less efficient. Proximal tubules use fatty acids via β-oxidation for maximal ATP production. Fatty acid metabolism in diseases like AKI and diabetic nephropathy can impair ATP production and mitochondrial function. Antioxidant defenses, including SOD2, catalase, and glutathione, protect mitochondria from ROS. Uncoupling proteins like UCP2 reduce ROS production. Hypoxia activates HIF1α, altering ETC efficiency. Nutrient-sensing pathways like mTOR and AMPK regulate mitochondrial biogenesis. mTORC1 activates PGC1α, while AMPK stimulates mitochondrial biogenesis and energy production. AMPK also inhibits mTORC1 under nutrient deprivation. Mitochondrial homeostasis requires balance between biogenesis, fission, fusion, and mitophagy. PGC1α regulates mitochondrial biogenesis and function. SIRT1 and SIRT3 deacetylate proteins involved in mitochondrial processes. cAMP and cGMP pathways also regulate mitochondrial biogenesis. Mitochondrial dynamics involve fission and fusion, with mitophagy removing damaged mitochondria. PINK1-PARKIN pathway tags mitochondria for degradation. Mitochondrial dysfunction in diseases like AKI and diabetic nephropathy disrupts