Regulation Mechanisms and Signaling Pathways of Autophagy

By Congcong He, D. Klionsky. Annual Review of Genetics, 2009

3,642 citations recorded by the source corpus.

Autophagy is a process of self-degradation of cellular components in which double-membrane autophagosomes sequester organelles or portions of cytosol and fuse with lysosomes or vacuoles for breakdown by resident hydrolases. Autophagy is upregulated in response to extra- or intracellular stress and signals such as starvation, growth factor deprivation, ER stress, and pathogen infection. Defective autophagy plays a significant role in human pathologies, including cancer, neurodegeneration, and infectious diseases. We present our current knowledge on the key genes composing the autophagy machinery in eukaryotes from yeast to mammalian cells and the signaling pathways that sense the status of different types of stress and induce autophagy for cell survival and homeostasis. We also review the recent advances on the molecular mechanisms that regulate the autophagy machinery at various levels, from transcriptional activation to post-translational protein modification.

Subfields: Cell Biology, Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/31b5dacf7d27d418fbdc94e38b79a7cf21c8fb31

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

In Epidemiology

In Physiology

Citations in the corpus

Autophagy: Renovation of Cells and Tissues (2011, background): “Limitation of various types of nutrients, such as amino acids, growth factors, oxygen, and energy, can induce autophagy (He and Klionsky, 2009; Kroemer et al., 2010).”
MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB (2012, background): “In addition, many cellular pathways known to regulate autophagy merge on MTORC1.(9) Despite these insights, the contribution of MTORC1 to the regulated expression of autophagy genes has not been characterized.”
Lysosomal calcium signaling regulates autophagy via calcineurin and TFEB (2015, background): “PI(3,5)P(2) controls membrane trafficking by direct activation of mucolipin Ca2+ release channels in the endolysosome.”
Mechanisms of neuronal cell death in ischemic stroke and their therapeutic implications (2021, background): “BNIP3 is also a competitive substrate of Bcl‐2 and Beclin‐1 and therefore leads to the release of Beclin‐1 and the activation of autophagy.(157,158) It was observed that the Beclin‐1 protein level increased as early as 4 h and peaked at 24–72 h after a rat model of severe neonatal cerebral hypoxia‐i”
The regulation of autophagy – unanswered questions (2011, background): “The role of the Atg1 complex in autophagy induction The Atg1 complex is an essential component for autophagy induction The Atg1 complex is involved in autophagy induction (see Box 1) and the target of rapamycin (TOR) – specifically, TOR complex 1 (TORC1) – is an upstream negative regulator of this c”
Autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity (2012, background): “Nanomaterials may induce autophagy through an oxidative stress mechanism [1], such as accumulation of oxidatively damaged proteins and subsequent endoplasmic reticulum stress, or mitochondrial damage [22].”
Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions (2022, background): “Signaling pathways related to autophagy in stroke Autophagy is a self-protective pathway that maintains cell homeostasis and promotes cell survival by degrading circulating long-lived proteins, misfolded and aggregated proteins, and damaged organelles to obtain energy or in response to cellular stre”
Autophagy Failure in Alzheimer's Disease – Locating the Primary Defect (2011, background): “This process is regulated by signaling cascades mediated through the liver kinase B1 (LKB1)/AMPactivated protein kinase (AMPK) or the class I phosphatidylinositol 3-kinase (PI3K)/Akt pathways which converge on the mammalian target of rapamycin (mTOR) kinase through TSC/Rheb (tuberous sclerosis compl”
Reactive Oxygen Species in Inflammation and Tissue Injury (2014, neutral): “Autophagy/mitophagy indirectly regulates intracellular oxidative stress by clearance of dysfunctional mitochondria and damaged proteins (170).”