You are what you eat: multifaceted functions of autophagy during C. elegans development - PubMed (original) (raw)
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You are what you eat: multifaceted functions of autophagy during C. elegans development
Peiguo Yang et al. Cell Res. 2014 Jan.
Abstract
Autophagy involves the sequestration of a portion of the cytosolic contents in an enclosed double-membrane autophagosomal structure and its subsequent delivery to lysosomes for degradation. Autophagy activity functions in multiple biological processes during Caenorhabditis elegans development. The basal level of autophagy in embryos removes aggregate-prone proteins, paternal mitochondria and spermatid-specific membranous organelles (MOs). Autophagy also contributes to the efficient removal of embryonic apoptotic cell corpses by promoting phagosome maturation. During larval development, autophagy modulates miRNA-mediated gene silencing by selectively degrading AIN-1, a component of miRNA-induced silencing complex, and thus participates in the specification of multiple cell fates controlled by miRNAs. During development of the hermaphrodite germline, autophagy acts coordinately with the core apoptotic machinery to execute genotoxic stress-induced germline cell death and also cell death when caspase activity is partially compromised. Autophagy is also involved in the utilization of lipid droplets in the aging process in adult animals. Studies in C. elegans provide valuable insights into the physiological functions of autophagy in the development of multicellular organisms.
Figures
Figure 1
The hierarchical recruitment of receptor and scaffold proteins triggers selective degradation of protein aggregates. In degradation of PGL granules, methylated PGL-1 and PGL-3 are recruited into SEPA-1 aggregates, which associate with the scaffold protein EPG-2. The scaffold protein EPG-7 mediates the degradation of AIN-1 and also of SQST-1. The cargo/receptor/scaffold complex triggers the formation of surrounding autophagosomal membranes. EPG-2 and EPG-7 directly interact with multiple ATG proteins, including LGG-1/Atg8. SEPA-1, AIN-1 and SQST-1 also interact with LGG-1.
Figure 2
Autophagic degradation of paternal mitochondria and MOs after fertilization. Schematic of the C. elegans spermatogenesis process. The two secondary spermatocytes may or may not remain attached by a cytoplasmic bridge. The cytosolic components are differentially segregated into developing spermatids and the residual body. Spermatids inherit mitochondria, Golgi-derived fibrous body-membranous organelles (FB-MOs) and a haploid nucleus, while the residual body contains all ribosomes, nearly all actin and myosin and most of the tubulin. Once spermatids bud from the residual body, the FB-MO complex is reorganized and FBs disappear. Sperm mitochondria and MOs are degraded by autophagy after fertilization. Residual bodies are engulfed and degraded by the gonadal sheath cells.
Figure 3
Autophagy, lipolysis and aging. The expression of LIPL-4 is activated by DAF-16. Autophagy and LIPL-4 are interdependently regulated. In response to nutrient availability, HLH-30 acts antagonistically to MXL-3 to regulate the expression of lysosomal lipases, including LIPL-1 and LIPL-3. Enhanced lipid metabolism extends lifespan of animals.
References
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