Prkn, also known as parkin RBR E3 ubiquitin protein ligase, is a key gene involved in the PINK1-PRKN pathway which governs mitophagy, a crucial process for eliminating damaged mitochondria. Mitophagy is essential for maintaining cellular homeostasis and is implicated in various biological processes and disease states. Genetic models, such as knockout mouse models, are valuable tools for studying Prkn's function.

In COPD pathogenesis, prkn knockout (KO) mice exposed to cigarette smoke showed enhanced airway wall thickening with emphysematous changes, accumulation of damaged mitochondria, increased oxidative modifications, and accelerated cellular senescence in airway epithelial cells compared to wild-type mice. In vitro, PRKN overexpression could induce mitophagy during CSE exposure even with reduced PINK1 levels, while PINK1 overexpression couldn't recover impaired mitophagy from PRKN knockdown, suggesting PRKN levels are rate-limiting in PINK1-PRKN-mediated mitophagy during CSE exposure [1].

In triple-negative breast cancer, hypoxia-induced GPCPD1 depalmitoylation regulated PRKN-mediated ubiquitination of VDAC1 to trigger mitophagy, and GPCPD1-mediated mitophagy promoted tumor growth and metastasis [2]. USP33, localized at the outer membrane of mitochondria, deubiquitinates PRKN, and its deficiency enhanced PRKN ubiquitination and mitophagy, protecting SH-SY5Y cells from neurotoxin-induced apoptosis [3].

In conclusion, Prkn plays a vital role in regulating mitophagy, which is crucial for maintaining cellular health. The study of Prkn using KO mouse models has provided significant insights into its role in diseases like COPD, highlighting its potential as a therapeutic target for such conditions.