Mitochondrial Dynamics in Renal Pathophysiology and Oxidative Stress

Mitochondria in renal tubular cells are dynamic organelles that continually undergo fission and fusion to adapt to fluctuating energy demands and to maintain quality control. Disruption of these dynamics contributes to the pathogenesis of both acute and chronic kidney disorders by promoting oxidative stress, bioenergetic failure and maladaptive inflammatory signalling. Excessive fragmentation of mitochondria impairs ATP generation, increases reactive oxygen species production and triggers mitochondrial DNA release, fuelling inflammatory cascades. Conversely, insufficient removal of damaged mitochondria through mitophagy leads to organelle accumulation, further compromising cellular health. In renal ischaemia–reperfusion injury, diabetic nephropathy and drug-induced nephrotoxicity, imbalances in fission-fusion proteins, defective mitophagy and altered biogenesis converge to exacerbate tubular injury and fibrotic progression. Understanding the molecular regulators of these processes has revealed novel targets for restoring mitochondrial integrity, attenuating oxidative damage and improving renal outcomes.

Research from Nature Portfolio

Recent studies have demonstrated that loss of Transforming Growth Factor-β receptor II in proximal tubule cells exacerbates mitochondrial injury and inflammatory activation in models of chronic kidney disease. Spatial transcriptomics and bulk RNA sequencing revealed that impaired TGF-β signalling leads to downregulation of complex I subunits, defective mitochondrial quality control and a metabolic shift towards aerobic glycolysis. These organelle defects promote maladaptive macrophage and dendritic cell recruitment, linking tubular mitochondrial dysfunction to interstitial inflammation in both murine and human disease. Restoration of receptor expression preserves mitochondrial homeostasis and suggests therapeutic avenues to slow disease progression.

Mitochondrial Dynamics in Renal Pathophysiology and Oxidative Stress publication trend

The graph below shows the total number of articles in mitochondrial dynamics in renal pathophysiology and oxidative stress across all publications each year (not limited to Nature Index journals).

Technical terms

Mitochondrial dynamics: The processes of mitochondrial fission and fusion that regulate organelle shape, distribution and function.

Mitophagy: The selective autophagic clearance of damaged mitochondria to maintain cellular health.

Reactive oxygen species (ROS): Chemically reactive oxygen derivatives that, in excess, damage proteins, lipids and nucleic acids.

Drp1: A dynamin-related GTPase responsible for mitochondrial fission by constricting the outer membrane.

Extracellular vesicles (EVs): Membrane-bound particles released by cells that transfer proteins, lipids and nucleic acids between cells.

Transforming growth factor-β (TGF-β): A cytokine that regulates cell growth, differentiation and mitochondrial quality control.

YME1L1: An ATP-dependent inner mitochondrial membrane protease that mediates protein turnover and energy metabolism.

References

1. Intrinsic TGF-β signaling attenuates proximal tubule mitochondrial injury and inflammation in chronic kidney disease. Nature Communications (2023).
2. Nitric oxide-primed engineered extracellular vesicles restore bioenergetics in acute kidney injury via mitochondrial transfer. Theranostics (2025).
3. SREBP1c‐Mediated Transcriptional Repression of YME1L1 Contributes to Acute Kidney Injury by Inducing Mitochondrial Dysfunction in Tubular Epithelial Cells. Advanced Science (2024).
4. Inhibition of Drp1- Fis1 interaction alleviates aberrant mitochondrial fragmentation and acute kidney injury. Cellular & Molecular Biology Letters (2024).