TABLE 1

The phenotypes and diseases associated with alteration of the autophagy genes

Genotype of the Autophagy-Related Genes	Phenotype	Relevant Diseases	Reference
	Protective Autophagy
Beclin1 deletion	Mice show an increased frequency of spontaneous tumors.	Breast, ovarian, and prostate cancer	Liang et al., 1999; Qu et al., 2003; Yue et al., 2003
Beclin1 overexpression	Decreases occur in MCF-7 cellular proliferation, in vitro clonogenicity, and tumorigenesis in nude mice.	Breast cancer	Liang et al., 1999
Atg5 deletion or the liver-specific Atg7 deficiency	Mice develop benign tumors in the liver.	Liver cancer	Takamura et al., 2011
Atg4C deficiency	Mice show increased chemically induced fibrosarcomas.	Fibrosarcomas	Marino et al., 2007
Bif-1deficiency	Mice show an increased frequency of spontaneous lymphomas.	Lymphomas	Takahashi et al., 2007
UVRAG overexpression	Significant tumor mass reduction occurs in mice.	Colon cancer	Liang et al., 2006
	Protective Autophagy
Atg7 mutation	Mice show impaired glucose tolerance and a decreased level of serum insulin.	Diabetes	Jung et al., 2008
	Protective Autophagy
Atg5 deficiency	Mice show cardiac hypertrophy and contractile dysfunction.	Cardiomyopathy	Nakai et al., 2007
LAMP2 deficiency	Cardiac myocytes are ultrastructurally abnormal, and heart contractility is severely reduced.	Danon disease	Nishino et al., 2000; Tanaka et al., 2000
Beclin1 deficiency	Mice show greater intracellular aggregate accumulation and hastened heart failure.	Heart disease	Tannous et al., 2008
Beclin1 or Atg5 overexpression	Enhanced autophagy significantly reduced apoptosis in cardiac HL-1 cells after ischemia/reperfusion.	Heart disease	Hamacher-Brady et al., 2006, 2007
	Autophagic Cell Death
Beclin1 knockdown	Inhibition of autophagy enhanced cell survival in cardiac myocytes in response to ischemia/reperfusion.	Heart disease	Valentim et al., 2006
Disruption or overexpression of Beclin1	Inhibition or promotion of autophagy diminished or accentuated the pathogenesis of load-induced heart failure in mice.	Cardiac hypertrophy	Zhu et al., 2007
	Protective Autophagy
Atg7 or Atg5 deficiency	Mice displayed ubiquitinated protein aggregates and inclusion bodies in their neurons.	Neurodegenerative disease	Hara et al., 2006; Komatsu et al., 2006
Ambra1 deficiency	Mice showed severe neural tube defects.	Neurodegenerative disease	Fimia et al., 2007
	Protective Autophagy
Beclin1 deficiency	Accelerated amyloid-β accumulation occurs.	Alzheimer disease	Pickford et al., 2008
	Protective Autophagy
Beclin1 overexpression	The accumulation of α-syn and the associated neuronal pathology are reduced in neuronal cells and a mouse model.	Parkinson disease	Spencer et al., 2009
	Protective Autophagy
Bec-1, Ce-atg7, or Ce-atg18 knockdown	The aggregate formation and toxicity of polyQ expansion proteins were increased in C. elegans.	Huntington disease	Jia et al., 2007
	Protective Autophagy
Beclin 1 overexpression	The brains of mice infected with Sindbis virus have fewer Sindbis virus RNA-positive cells, fewer apoptotic cells, and lower viral titers	Infectious disease	Liang et al., 1998
Atg5 deficiency	Dendritic cells show impaired autophagic delivery to endosomal Toll-like receptors and interferon production during virus infection.	Infectious diseases	Lee et al., 2007
Atg5 deficiency	Periphery CD8⁺ T cells display increased apoptosis, and CD4⁺ and CD8⁺ T cells show defective activation-induced proliferation.	Infectious diseases	Pua et al., 2007
	Protective Autophagy
Bec-1 or Ce-atg7 deficiency	The mean and maximum life span of C. elegans were decreased.	Aging	Jia and Levine, 2007
	Protective Autophagy
IRGM and ATG16L1	A genomewide association scan in individuals with Crohn disease identified IRGM and ATG16L1 as new risk loci.	Immune disease	Massey and Parkes, 2007; Parkes et al., 2007
	Protective Autophagy
Beclin1 overexpression	Restoration of autophagy rescued the disease phenotype in cystic fibrosis epithelial cells.	Inflammation	Luciani et al., 2010