Molecular mechanism and regulation of autophagy.
Autophagy is a major cellular pathway for the degradation of long-lived proteins and cytoplasmic organelles in eukaryotic cells. A large number of intracellular/extracellular stimuli, including amino acid starvation and invasion of microorganisms, are able to induce the autophagic response in cells. The discovery of the ATG genes in yeast has greatly advanced our understanding of the molecular mechanisms participating in autophagy and the genes involved in regulating the autophagic pathway. Many yeast genes have mammalian homologs, suggesting that the basic machinery for autophagy has been evolutionarily conserved along the eukaryotic phylum. The regulation of autophagy is a very complex process. Many signaling pathways, including target of rapamycin (TOR) or mammalian target of rapamycin (mTOR), phosphatidylinositol 3-kinase-I (PI3K-I)/PKB, GTPases, calcium and protein synthesis all play important roles in regulating autophagy. The molecular mechanisms and regulation of autophagy are discussed in this review.
Yang
Ya-Ping
YP
Department of Pharmacology, Soochow University School of Medicine, Suzhou 215007, China.
Liang
Zhong-Qin
ZQ
Gu
Zhen-Lun
ZL
Qin
Zheng-Hong
ZH
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000502:physiology; D009369:Neoplasms / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology*; D011489:Protein Denaturation / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology*; D011506:Proteins / Q000502:physiology; D015398:Signal Transduction; D025841:Small Ubiquitin-Related Modifier Proteins; D058570:TOR Serine-Threonine Kinases
D000596:Amino Acids; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D002118:Calcium; D008869:Microtubule-Associated Proteins; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D011506:Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D058570:TOR Serine-Threonine Kinases; C466624:ATG12 protein, human; C502778:ATG5 protein, human; C546842:MTOR protein, human