Regulation of cell growth by autophagy.
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-beta (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.
Vellai
Tibor
T
Department of Genetics, Eötvös Loránd University, Budapest, Hungary. vellai@falco.elte.hu
Bicsák
Bertalan
B
Tóth
Márton L
ML
Takács-Vellai
Krisztina
K
Kovács
Attila L
AL
D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D049108:Cell Enlargement; D048429:Cell Size; D051858:Forkhead Transcription Factors; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C108831:daf-16 protein, C elegans; D007334:Insulin-Like Growth Factor I; C112443:UNC-51 protein, C elegans; D017346:Protein Serine-Threonine Kinases