Autophagy, selective autophagy, and necroptosis in COPD

Figures & data

Table 1 Roles of selective autophagy in COPD

Cell death mode	Strain/manipulation	Phenotype/observation	Reference
Mitophagy	PINK1^−/− mice, chronic and acute CS	Decreased epithelial cell necroptosis and airspace enlargement. Decreased airway dysfunction	^Citation41
	C57Bl/6, acute CS	Injection of mitophagy inhibitor Mdivi-1 ameliorated CS-dependent airway dysfunction	^Citation41
	Human COPD lung	Increased mitophagy markers	^Citation41
Ciliophagy	Becn1^+/− mice, acute CS	Decreased cilia loss and airway dysfunction	^Citation19

Abbreviations: CS, cigarette smoke; PINK1, PTEN-induced putative kinase protein 1.

Table 2 Role of necroptosis in COPD

Cell death mode	Strain/manipulation	Phenotype/observation	Reference
Necroptosis	C57BL/6, chronic CS	Increased necroptosis markers	^Citation41
	mBE-mtor^−/− mice, chronic CS	Decreased necroptosis markers and airspace enlargement	^Citation47
	BALB/cByJ, acute CS	Increased neutrophilic airway inflammation	^Citation46
	Human COPD lung	Increased necroptosis markers	^Citation41

Abbreviation: CS, cigarette smoke.

Figure 1 Mitophagy and necroptosis in COPD.

Notes: CS-induced mitochondrial fission and PINK1-dependent mitophagy in epithelial cells are independent of mitochondrial integrity. Aberrant mitophagy may increase the population of impaired mitochondria, leading to induction of necrosome formation. In the necrosome, RIP3 phosphorylates MLKL, and translocation of phosphorylated MLKL to the cell membrane leads to direct pore formation and epithelial cell death with the release of DAMPs.
Abbreviations: CS, cigarette smoke; DAMP, damage-associated molecular pattern; MLKL, mixed-lineage kinase domain-like protein; PINK1, PTEN-induced putative kinase protein 1.

Figure 2 Ciliophagy in COPD.

Notes: CS-induced oxidative stress leads to cilia protein damage. Damaged cilia proteins are ubiquitinated, which promotes aggregate formation. HDAC6 recognizes ubiquitinated protein aggregates and delivers them to autophagosomes. This degradation of cilia proteins, through an autophagy-dependent process termed “ciliophagy,” is associated with cilia shortening.
Abbreviations: CS, cigarette smoke; HDAC6, histone deacetylase 6.

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