Autoimmune kidney diseases, including Membranous Nephropathy (MN), Lupus Nephritis (LN), and ANCA - Associated Nephritis, are major contributors to chronic kidney disease and end - stage renal disease globally. Mitochondria, as the powerhouses of cells, play crucial roles in maintaining cellular homeostasis and immune regulation. However, the specific mechanisms by which mitochondrial dysfunction participates in the pathogenesis of these three autoimmune kidney diseases remain poorly understood. This review aims to systematically summarize the current research progress on the involvement of mitochondrial dysfunction in MN, LN, and ANCA - Associated Nephritis, and to explore potential therapeutic targets based on mitochondrial biology.

A comprehensive literature search was conducted in PubMed, Web of Science, and Embase databases using keywords such as "mitochondrial", "membranous nephropathy", "lupus nephritis", "ANCA - associated nephritis", "pathogenesis", and "therapeutic targets". The data extraction focused on the structural and functional changes of mitochondria in different autoimmune kidney diseases, the molecular mechanisms linking mitochondrial dysfunction to immune dysregulation, and potential therapeutic strategies targeting mitochondria.

In MN, mitochondrial dysfunction has been identified in podocytes, which are key cells in the glomerular filtration barrier. Studies have shown that podocytes in MN patients exhibit abnormal mitochondrial morphology, such as cristae fragmentation and swelling, and reduced mitochondrial membrane potential. These structural and functional abnormalities lead to decreased ATP production, increased reactive oxygen species (ROS) generation, and impaired podocyte function. For LN, LN is a renal manifestation of systemic lupus erythematosus (SLE), characterized by immune complex deposition and immune system activation. Mitochondrial dysfunction plays a critical role in the pathogenesis of LN. Glomerular cells, including podocytes and endothelial cells, in LN patients show mitochondrial structural damage, such as cristae loss and matrix vacuolization, and impaired mitochondrial function, including reduced oxidative phosphorylation and increased ROS production. Mitochondrial DNA (mtDNA) released from damaged mitochondria can act as a damage - associated molecular pattern (DAMP), activating the innate immune system and promoting inflammation. Moreover, autoantibodies against mitochondrial components have been detected in LN patients, further exacerbating mitochondrial damage and immune dysregulation. ANCA -associated nephritis is another autoimmune disease mediated by anti - neutrophil cytoplasmic antibodies (ANCA). Mitochondrial dysfunction in neutrophils and monocytes is involved in the pathogenesis of this disease. ANCA can activate neutrophils, leading to mitochondrial ROS burst and mtDNA release. The released mtDNA can form neutrophil extracellular traps (NETs), which further promote inflammation and tissue damage. Additionally, mitochondrial dysfunction in renal tubular epithelial cells contributes to tubular injury and interstitial fibrosis in ANCA - associated nephritis.

Mitochondrial dysfunction is a common and crucial pathological mechanism in MN, LN, and ANCA - associated nephritis. Structural and functional abnormalities of mitochondria in different renal cells lead to impaired cellular function, immune dysregulation, and inflammation, ultimately contributing to the progression of these autoimmune kidney diseases. Targeting mitochondrial dysfunction, such as restoring mitochondrial structure and function, inhibiting ROS production, and modulating immune cell metabolism, holds great promise as a novel therapeutic strategy for autoimmune kidney diseases. Further research is needed to fully elucidate the specific molecular mechanisms underlying mitochondrial dysfunction in each disease and to develop more targeted and effective therapeutic approaches.