Selective Autophagy in Kidney Diseases: The Tip of the Iceberg

Autophagy is a conserved degradation process dependent on lysosomes and is essential for maintaining homeostasis in eukaryotic cells. Dysfunctional autophagy can lead to the development and progression of kidney diseases, although the precise mechanisms remain to be completely understood. Recent studies have demonstrated that damaged organelles and long-lived proteins can be selectively identified and degraded via the autophagy-lysosome pathway, a process known as selective autophagy. This process is mediated by various molecules, including sensors, adaptors, and autophagy receptors, and can occur through both ubiquitin-dependent and -independent pathways. Selective autophagy is classified based on the specific substrates targeted for degradation, including mitophagy (mitochondria), pexophagy (peroxisomes), lysophagy (lysosomes), ER-phagy (endoplasmic reticulum), lipophagy (lipid droplets), aggrephagy (protein aggregates), ferritinophagy (ferritin), and other organelle-specific forms. These pathways are recognized as being closely involved in the pathophysiology of various kidney diseases. Modulating selective autophagy through traditional Chinese medicine or compounds, such as autophagosome-tethering compounds, presents a promising therapeutic approach for renal disorders. This narrative review summarizes recent advancements in understanding the molecular mechanisms linking selective autophagy to kidney diseases and explores emerging therapies that target these pathways to enhance clinical outcomes.