Редактирование: PRKN (раздел)

==Publications==

{{medline-entry
|title=[[PRKN]]-regulated mitophagy and cellular senescence during COPD pathogenesis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30290714
|abstract=Cigarette smoke ([[CS]])-induced accumulation of mitochondrial damage has been widely implicated in chronic obstructive pulmonary disease (COPD) pathogenesis. Mitophagy plays a crucial role in eliminating damaged mitochondria, and is governed by the [[PINK1]] ([[PTEN]] induced putative protein kinase 1)-[[PRKN]] (parkin RBR E3 ubiquitin protein ligase) pathway. Although both increased [[PINK1]] and reduced [[PRKN]] have been implicated in COPD pathogenesis in association with mitophagy, there are conflicting reports for the role of mitophagy in COPD progression. To clarify the involvement of [[PRKN]]-regulated mitophagy in COPD pathogenesis, prkn knockout (KO) mouse models were used. To illuminate how [[PINK1]] and [[PRKN]] regulate mitophagy in relation to [[CS]]-induced mitochondrial damage and cellular senescence, overexpression and knockdown experiments were performed in airway epithelial cells (AEC). In comparison to wild-type mice, prkn KO mice demonstrated enhanced airway wall thickening with emphysematous changes following [[CS]] exposure. AEC in [[CS]]-exposed prkn KO mice showed accumulation of damaged mitochondria and increased oxidative modifications accompanied by accelerated cellular senescence. In vitro experiments showed [[PRKN]] overexpression was sufficient to induce mitophagy during [[CS]]E exposure even in the setting of reduced [[PINK1]] protein levels, resulting in attenuation of mitochondrial ROS production and cellular senescence. Conversely [[PINK1]] overexpression failed to recover impaired mitophagy caused by [[PRKN]] knockdown, indicating that [[PRKN]] protein levels can be the rate-limiting factor in [[PINK1]]-[[PRKN]]-mediated mitophagy during [[CS]]E exposure. These results suggest that [[PRKN]] levels may play a pivotal role in COPD pathogenesis by regulating mitophagy, suggesting that [[PRKN]] induction could mitigate the progression of COPD. Abbreviations: AD: Alzheimer disease; AEC: airway epithelial cells; BALF: bronchoalveolar lavage fluid; AKT: AKT serine/threonine kinase; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CDKN1A: cyclin dependent kinase inhibitor 1A; CDKN2A: cyclin dependent kinase inhibitor 2A; COPD: chronic obstructive pulmonary disease; [[CS]]: cigarette smoke; [[CS]]E: [[CS]] extract; CXCL1: C-X-C motif chemokine ligand 1; CXCL8: C-X-C motif chemokine ligand 8; HBEC: human bronchial epithelial cells; 4-HNE: 4-hydroxynonenal; IL: interleukin; KO: knockout; LF: lung fibroblasts; LPS: lipopolysaccharide; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; 8-OHdG: 8-hydroxy-2'-deoxyguanosine; OPTN: optineurin; [[PRKN]]: parkin RBR E3 ubiquitin protein ligase; PCD: programmed cell death; PFD: pirfenidone; PIK3C: phosphatidylinositol-4:5-bisphosphate 3-kinase catalytic subunit; [[PINK1]]: [[PTEN]] induced putative kinase 1; [[PTEN]]: phosphatase and tensin homolog; RA: rheumatoid arthritis; ROS: reactive oxygen species; SA-GLB1/β-Gal: senescence-associated-galactosidase, beta 1; SASP: senescence-associated secretory phenotype; SNP: single nucleotide polymorphism; TNF: tumor necrosis factor.
|mesh-terms=* Animals
* Cell Cycle Proteins
* Cell Line
* Cellular Senescence
* Cigarette Smoking
* Disease Models, Animal
* Epithelial Cells
* Humans
* Lung
* Membrane Transport Proteins
* Mice
* Mice, Inbred C57BL
* Mice, Knockout
* Microscopy, Electron
* Mitochondria
* Mitophagy
* Nuclear Proteins
* PTEN Phosphohydrolase
* Protein Kinases
* Pulmonary Disease, Chronic Obstructive
* Pyridones
* Reactive Oxygen Species
* Ubiquitin-Protein Ligases
|keywords=* COPD
* Cellular senescence
* PINK1
* PRKN
* mitophagy
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351145
}}