Impairment of starvation-induced and constitutive autophagy in <i>Atg7</i>-deficient mice

Komatsu, Masaaki; Waguri, Satoshi; Ueno, Takashi; Iwata, Junichi; Murata, Shigeo; Tanida, Isei; Ezaki, Junji; Mizushima, Noboru; Ohsumi, Yoshinori; Uchiyama, Yasuo; Kominami, Eiki; Tanaka, Keiji; Chiba, Tomoki

doi:10.1083/jcb.200412022

Cited by 2,202 publications

(2,222 citation statements)

References 50 publications

Supporting

Mentioning

2,105

Contrasting

Unclassified

Order By: Relevance

“…Recently, it has been observed that the hepatocytes of liver-specific conditional Atg7 KO mice develop ubiquitin-positive aggregates. 14 We also observed such aggregates in Atg5 À/À neonates (unpublished data). These findings suggest that baseline autophagy is critical for intracellular clearance ( Figure 3).…”

Section: Intracellular Clearance By 'Baseline Autophagy': Antidegenermentioning

confidence: 52%

The pleiotropic role of autophagy: from protein metabolism to bactericide

2005

View full text Add to dashboard Cite

Autophagy is in principle a nonselective, bulk degradation system within cells, with a contribution to intracellular protein degradation estimated to be as large as that of the ubiquitin--proteasome system. The primary roles of autophagy are baseline turnover of intracellular proteins and organelles, production of amino acids in nutrient emergency, and regression of retired tissues. These functions guarantee rejuvenation and adaptation to adverse conditions, and even underlie dynamic processes such as development/metamorphosis. In addition, several other roles for autophagy have recently been discovered, such as presentation of endogenous antigens and degradation of invasive bacteria. This review will discuss the biological significance of autophagy from yeast to higher eukaryotes.

show abstract

Section: Intracellular Clearance By 'Baseline Autophagy': Antidegenermentioning

confidence: 52%

The pleiotropic role of autophagy: from protein metabolism to bactericide

2005

View full text Add to dashboard Cite

show abstract

“…Similar to the systemic atg7 KO mice, ATG5i mice on dox appeared smaller in size with smaller weight gain in both genders (Figure 1(c)). Anatomical inspection revealed, as in the whole-body somatic atg7 KO mice and/or atg5 and atg7 KO mice, a reduction of fat [16] and muscle tissues (Figures 1(d,e)) [17], with the presence of hepatomegaly [9], splenomegaly, and seminal vesicle atrophy (Figure 1(fh)) [18]. …”

Section: Resultsmentioning

confidence: 99%

“…This coincides with a period of metabolic stress wherein neonates must adapt and engage the autophagic machinery to mobilise their own food stores [8,9]. Additionally, conditional whole-body knockout of Atg7 in adult mice has provided further evidence for the requirement of autophagy to survive acute metabolic stress.…”

Section: Introductionmentioning

confidence: 99%

A novel Atg5-shRNA mouse model enables temporal control of Autophagy in vivo

et al. 2018

View full text Add to dashboard Cite

Macroautophagy/autophagy is an evolutionarily conserved catabolic pathway whose modulation has been linked to diverse disease states, including age-associated disorders. Conventional and conditional whole-body knockout mouse models of key autophagy genes display perinatal death and lethal neurotoxicity, respectively, limiting their applications for in vivo studies. Here, we have developed an inducible shRNA mouse model targeting Atg5, allowing us to dynamically inhibit autophagy in vivo, termed ATG5i mice. The lack of brain-associated shRNA expression in this model circumvents the lethal phenotypes associated with complete autophagy knockouts. We show that ATG5i mice recapitulate many of the previously described phenotypes of tissue-specific knockouts. While restoration of autophagy in the liver rescues hepatomegaly and other pathologies associated with autophagy deficiency, this coincides with the development of hepatic fibrosis. These results highlight the need to consider the potential side effects of systemic anti-autophagy therapies.

show abstract

“…These data indicated that autophagosome formation plays a critical anti-apoptosis role during PPRV infection. Moreover, the expression products of the ATG7 and Beclin-1 genes are essential for the activation of autophagosome formation, and knocking down the ATG7 and Beclin-1 genes can impair the autophagic pathway [70,71]. Interestingly, Beclin-1 is required for ATG7-dependent and ATG7-independent autophagy [72].…”

Section: Discussionmentioning

confidence: 99%

Autophagy enhances the replication of Peste des petits ruminants virus and inhibits caspase-dependent apoptosis in vitro

Yang

Xue

et al. 2018

Virulence

View full text Add to dashboard Cite

Peste des petits ruminants (PPR) is an acute and highly contagious disease in small ruminants that causes significant economic losses in developing countries. An increasing number of studies have demonstrated that both autophagy and apoptosis are important cellular mechanisms for maintaining homeostasis, and they participate in the host response to pathogens. However, the crosstalk between apoptosis and autophagy in host cells during PPRV infection has not been clarified. In this study, autophagy was induced upon virus infection in caprine endometrial epithelial cells (EECs), as determined by the appearance of double- and single-membrane autophagy-like vesicles, LC3-I/LC3-II conversion, and p62 degradation. We also found that PPRV infection triggered a complete autophagic response, most likely mediated by the non-structural protein C and nucleoprotein N. Moreover, our results suggest that autophagy not only promotes the replication of PPRV in EECs but also provides a potential mechanism for inhibiting PPRV-induced apoptosis. Inhibiting autophagosome formation by wortmannin and knocking down the essential autophagic proteins Beclin-1 and ATG7 induces caspase-dependent apoptosis in EECs in PPRV infection. However, inhibiting autophagosome and lysosome fusion by NH4Cl and chloroquine did not increase the number of apoptotic cells. Collectively, these data are the first to indicate that PPRV-induced autophagy inhibits caspase-dependent apoptosis and thus contributes to the enhancement of viral replication and maturity in host cells.

show abstract

Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice

Cited by 2,202 publications

References 50 publications

The pleiotropic role of autophagy: from protein metabolism to bactericide

The pleiotropic role of autophagy: from protein metabolism to bactericide

A novel Atg5-shRNA mouse model enables temporal control of Autophagy in vivo

Autophagy enhances the replication of Peste des petits ruminants virus and inhibits caspase-dependent apoptosis in vitro

Contact Info

Product

Resources

About