Autophagy Genes unc-51 and bec-1 Are Required for Normal Cell Size in Caenorhabditis elegans

Aladzsity, István; Tóth, Márton L.; Sigmond, Tímea; Szabó, Emese; Bicsak, Bertalan; Barna, János; Regős, Ágnes; Orosz, László; Kovács, Attila; Vellai, Tibor

doi:10.1534/genetics.107.075762

Cited by 46 publications

(36 citation statements)

References 28 publications

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“…Autophagosome formation is compromised in unc-51 and bec-1 mutant worms. 14,15 This however does not exclude the possibility that in unc-51 and bec-1 mutant nematodes cell growth becomes retarded independently of abnormal autophagy. Thus, monitoring cell size in organisms in which autophagosome formation is specifically blocked with chemicals is a challenging area for future investigations.…”

Section: Autophagy Genes Are Required For Normal Cell Sizementioning

confidence: 96%

“…14 Mutant C. elegans strains deficient in UNC-51/Atg1 exhibit a small body size phenotype (Sma). The reduced body length of these animals results from a significant decrease in the size and volume of different cell types such as hypodermal and intestinal cells, which are known to primarily determine body size in this organism.…”

Section: Autophagy Genes Are Required For Normal Cell Sizementioning

confidence: 99%

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Regulation of cell growth by autophagy

et al. 2008

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Cell growth-the primary determinant of cell size-has an intimate relationship with proliferation; cells divide only after they reach a critical size. Despite its developmental and medical significance, little is known about cellular pathways that mediate the growth of cells. Accumulating evidence demonstrates a role for autophagy-a mechanism of eukaryotic cells to digest their own constituents during development or starvation-in cell size control. Increasing autophagic activity by prolonged starvation, rapamycin treatment inhibiting TOR (target of rapamycin) signaling, or genetic intervention, causes cellular atrophy in worms, flies and mammalian cell cultures. In contrast, we have shown that in the nematode Caenorhabditis elegans mutational inactivation of two autophagy genes, unc-51/Atg1 and bec-1/Atg6, confers reduced cell size. We argue that physiological levels of autophagy are required for normal cell size, whereas both insufficient and excessive levels of autophagy lead to retarded cell growth. Furthermore, we discuss data suggesting that the insulin/IGF-1 (insulin-like growth factor receptor-1) and TGF-β (transforming growth factor-beta) signaling systems acting as major growth regulatory pathways converge on autophagy genes to control cell size. Thus, autophagy may act as a central regulatory mechanism of cell growth.

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Section: Autophagy Genes Are Required For Normal Cell Sizementioning

confidence: 96%

Section: Autophagy Genes Are Required For Normal Cell Sizementioning

confidence: 99%

Regulation of cell growth by autophagy

et al. 2008

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“…Furthermore, certain autophagy genes have been reported to mediate the effects that insulin/IGF-1 and TGF-b signalling have on cell growth. 7,8 When autophagy gene activity is blocked, nematodes are unable to express a giant body-size phenotype induced by aberrant insulin/IGF-1 or TGF-b receptor activity. This indicates that these growth modulatory signalling pathways converge on autophagy genes to control cell size.…”

Section: Interaction Of Longevity Pathways With Autophagymentioning

confidence: 99%

“…However, when studying diminishing degradative pathways and their impact on ageing, one might meet two main difficulties. First, because protein degradation is essential for normal growth and development, [7][8][9][10][11][12][13] genetic manipulation interfering with these processes is likely to have pleiotropic effects, for example, it causes premature death, masking any possible specific role in ageing control. Second, uncovering novel genetic determinants of ageing is usually based on the recognition of longlived phenotype caused by reduced activity of pro-ageing genes ( Figure 1).…”

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confidence: 99%

Autophagy genes and ageing

2008

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Ageing in divergent animal phyla is influenced by several evolutionarily conserved signalling pathways, mitochondrial activity and various environmental factors such as nutrient availability and temperature. Although ageing is a multifactorial process with many mechanisms contributing to the decline, the intracellular accumulation of damaged proteins and mitochondria is a feature common to all aged cells. Autophagy (cellular self-eating) -a lysosome-mediated catabolic process of eukaryotic cells to digest their own constituents -is a major route for the bulk degradation of aberrant cytosolic macromolecules and organelles. Indeed, genetic studies show that autophagy-related genes are required for lifespan extension in various long-lived mutant nematodes and promote survival in worms and flies exposed to prolonged starvation. These data implicate autophagy in ageing control. Furthermore, results in Drosophila demonstrate that promoting basal expression of the autophagy gene Atg8 in the nervous system extends lifespan by 50%, thereby providing evidence that the autophagy pathway regulates the rate at which the tissues age. In this review, the molecular mechanisms by which autophagy genes interact with longevity pathways in diverse organisms ranging from yeast to mammals are discussed.

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“…7 In C. elegans, disruption of Atg1/unc-51 or Atg6/bec-1 led to a shorter body length and a reduction in cell size, and suppressed the increased body size of mutants in the IGF-1 and TGFβ pathways. 45 By what mechanisms might autophagy influence cell growth? A simple model in which bulk autophagic degradation of cytoplasm acts as a balance to macromolecular biosynthesis could explain the inverse correlation between autophagy and cell growth, and would fit well with observations of increased growth potential of autophagy deficient cells.…”

Section: Cell Growthmentioning

confidence: 99%

Eating on the fly: Function and regulation of autophagy during cell growth, survival and death in Drosophila

Neufeld¹,

Baehrecke²

2008

Autophagy

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Significant progress has been made over recent years in defining the normal progression and regulation of autophagy, particularly in cultured mammalian cells and yeast model systems. However, apart from a few notable exceptions, our understanding of the physiological roles of autophagy has lagged behind these advances, and identification of components and features of autophagy unique to higher eukaryotes also remains a challenge. In this review we describe recent insights into the roles and control mechanisms of autophagy gained from in vivo studies in Drosophila. We focus on potential roles of autophagy in controlling cell growth and death, and describe how the regulation of autophagy has evolved to include metazoan-specific signaling pathways. We discuss genetic screening approaches that are being used to identify novel regulators and effectors of autophagy, and speculate about areas of research in this system likely to bear fruit in future studies.

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Autophagy Genes unc-51 and bec-1 Are Required for Normal Cell Size in Caenorhabditis elegans

Cited by 46 publications

References 28 publications

Regulation of cell growth by autophagy

Regulation of cell growth by autophagy

Autophagy genes and ageing

Eating on the fly: Function and regulation of autophagy during cell growth, survival and death in Drosophila

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