Table 1.

Kidney disease phenotype after genetic ablation of autophagy/mitophagy-related genes in models of AKI and CKD

Setting	Targeted Pathway	Model	Targeted Gene	Targeted Tissue/Cell	Kidney Phenotypical Changes	Reference
AKI	Autophagy	Sepsis: LPS	Atg7	Proximal tubules	Exacerbated proximal tubular cell injury and worsening kidney function	35
			Atg7	Proximal tubules	Tubular cell apoptosis and impaired kidney function	36
			Atg5	Podocytes	Increased transient albuminuria	13
	Mitophagy	Sepsis: CLP, LPS	Pink1 or Prkn	Global	Increased mitochondrial fragmentation, tubular damage, apoptosis, serum creatinine, and BUN	37
	Autophagy	Cisplatin	Atg5	Proximal tubules	Increased DNA damage, apoptosis, oxidative stress, number of protein aggregates, tissue damage, and impaired kidney function	38
			Atg7	Proximal tubules	Exacerbated cell death, tissue damage, and impaired kidney function	39
	Mitophagy	Cisplatin	Pink1 or Prkn	Global	Increased tubular injury, apoptosis, serum creatinine, and BUN	40
			Pink1	Global	Reduced DRP1, tubular apoptosis, and kidney injury	41
	Autophagy	IRI	Atg5	Tubules	Increased tubular injury, apoptosis, and serum creatinine	16
			Atg5	Proximal tubules	Increased number of abnormal mitochondria, tubular cell death, kidney damage, serum creatinine, and BUN	42
			Atg7	Proximal tubules	Increased serum creatinine and BUN	39
			Atg7	Tubules	Reduced FGF2 expression and fibrotic responses	43
			Atg5	Tubules	Exacerbated kidney injury and tubulointerstitial fibrosis	44
			Atg5	Distal tubules	Increased fibrotic responses	44
			Becn1	Tubules	Exacerbated tissue damage, inflammation, tubulointerstitial fibrosis, and impaired kidney function	44
			Becn1	Distal tubules	Worsening kidney function	44
	Mitophagy	IRI	Pink1 or Prkn	Global	Exacerbated oxidative stress, inflammation, apoptosis, and mitochondrial damage in proximal tubules	45
			Mfn2	Proximal tubules	Increased cell survival and improved kidney function	46
CKD	Autophagy	Kidney fibrosis/UUO	Map1lc3a	Global	Increased TGF-β1 expression, collagen accumulation, and kidney fibrosis	47
			Atg5	Proximal tubules	Cell cycle arrested at the G2/M phase and increased tubulointerstitial fibrosis	48
			Atg5	Proximal tubules	Increased inflammation, NF-κB activation, infiltration of macrophages and T cells in the kidney	49
			Atg7	Distal tubules	Increased accumulation of abnormal mitochondria, apoptotic markers, NLRP3 inflammasome formation, and kidney fibrosis	50
			Atg7	Proximal tubules	Reduced tubular atrophy, nephron loss, macrophage infiltration, and kidney fibrosis	51
			Becn1	Global	Increased TGF-β1 expression and collagen accumulation	47
			Becn1	Tubules	Exacerbated collagen deposition and kidney fibrosis.	44
	Mitophagy	Kidney fibrosis/UUO or adenine diet	Pink1 or Prkn	Global	Increased kidney macrophage-derived mROS, tubulointerstitial fibrosis, and impaired kidney function	30
			Mfn2	Myeloid lineage	Impaired macrophage mitochondrial biogenesis, increased macrophage-derived fibrotic responses, kidney fibrosis, serum creatinine, and BUN	34
	Autophagy	DN/Akita mice	Atg7	Proximal tubules	Increased tubular hypertrophy, macrophage infiltration, and kidney fibrosis	52
		DN/high-fat diet	Atg5	Podocytes	Loss of podocytes and massive albuminuria	53
		DN/high glucose	Atg5	Podocytes	Podocyte apoptosis, leaky GFB, and glomerulosclerosis	17
		DN/STZ	Atg5	Endothelial cells	Capillary rarefactions, loss of fenestrations, and glomerular endothelial lesions	17
	Autophagy	Podocytopathies/PAN, adriamycin	Atg5	Podocytes	Increased accumulation of oxidized proteins linked to proteinuria, loss of podocytes, and glomerulosclerosis	13
		Podocytopathies/ unilateral nephrectomy	Atg7	Podocytes	ER stress, cytoskeletal destabilization, foot process effacement, and albuminuria	54

AKI, acute kidney injury; atg, autophagy-related; Becn1, beclin 1; BUN, blood urea nitrogen; CKD, chronic kidney disease; CLP, cecal ligation and puncture; DN, diabetic nephropathy; DRP1, dynamin-related protein 1; ER stress, endoplasmic reticulum-derived stress; FGF2, fibroblast growth factor 2; GFB, glomerular filtration barrier; IRI, ischemia-reperfusion injury; LPS, lipopolysaccharides; Map1lc3a, microtubule-associated protein 1 light chain 3α (LC3A); mROS, mitochondria-derived reactive oxygen species; PAN, puromycin aminonucleoside; Pink1, phosphatase and tensin homolog-induced kinase 1; Prkn, Parkin; STZ, streptozotocin; TGF-β1, transforming growth factor-β1; UUO, unilateral ureteral obstruction.