New Discoveries on Autophagy
- Impaired clearance of dying cells has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). A noncanonical autophagy pathway is known to engage LC3-associated phagocytosis (LAP), where autophagy elements are recruited to facilitate phagosomal maturation for cellular clearance. A new study discovers that the defects in noncanonical LAP, but not canonical autophagy, cause SLE-related pathology in mice. (Nature, 2016)
- Autophagy is a highly conserved cellular process. While the cytoplasmic components of autophagy have been progressively unveiled, transcriptional and epigenetic regulation of autophagy is poorly understood. The new findings demonstrate that the histone arginine methyltransferase CARM1 acts a critical co-activator of TFEB to initiate autophagy-related gene expression and that autophagy induction can be regulated by the AMPK-SKP2-CARM1 signaling axis, in response to cellular starvation. (Nature, 2016)
- Urolithins are metabolites of ellagitannins found in the pomegranate, nuts and berries. In this novel discovery, urolithins are found to improve fitness and extend lifespan of C. elegans. Urolithin A (UA) induces autophagy of mitochondria (mitophagy) and prevents accumulation of dysfunctional mitochondria. In rodents, UA improves the exercise capacity through mitophagy induction. These findings propose the medicinal potential of UA for improving mitochondrial and muscular function. (Nature Medicine, 2016)
Autophagy Dysregulation: Diseases and Genes
Condition |
Disease |
Genes |
Neurodegeneration |
Alzheimer's disease |
BECN1, PSEN1, APOE, APP, SNCA, ATP13A2 |
Parkinson's disease |
PARK2, PARK6 |
Huntington's disease |
HTT |
Inflammation |
Chrohn's disease |
ATG16L1, NOD2, IRGM |
Ulcerative colitis |
SMURF1 |
Malignancy |
Ovarian and prostate cancer |
BECN1 |
Colon cancer |
UVRAG, PARK2 |
Lung and brain cancer |
PARK2 |
Breast cancer |
BECN1, EI24/PIG8 |
Immune disorder |
Systemic lupus erythematosus |
ATG5 |
Childhood and adult asthma |
ATG5 |
Infection |
Tuberculosis |
IRGM |
Mammalian Authophagy (Macroautophagy) Pathway
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MTOR monoclonal antibody (M01), clone 2C5
H00002475-M01 |
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Proximity Ligation Analysis of protein-protein interactions between AKT1 and MTOR. HeLa cells were stained with anti-AKT1 (H00000207-D01P) rabbit purified polyclonal (1:1200) and anti-MTOR mouse monoclonal antibody (1:50). Each red dot represents the detection of protein-protein interaction complex, and nuclei were counterstained with DAPI (blue). |
SQSTM1 monoclonal antibody (M01), clone 2C11
H00007474-M04 |
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Immunofluorescence of monoclonal antibody to SQSTM1 on HeLa cell. [antibody concentration 10 ug/ml]. |
PRKAA2 monoclonal antibody (M02), clone 1G8
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Proximity Ligation Analysis of protein-protein interactions between STK11 (H00006794 – D01P) and PRKAA2. HeLa cells were stained with anti-STK11 rabbit purified polyclonal (1:1200) and anti-PRKAA2 mouse monoclonal antibody (1:50). Each red dot represents the detection of protein-protein interaction complex, and nuclei were counterstained with DAPI (blue). |
| References |
Jennifer Martinez, et al. (2016) Nature. DOI: 10.1038/nature17950
Hi-Jai R Shin, et al. (2016) Nature. DOI:10.1038/nature18014
Dongryeol Ryu, et al. (2016). Nature Medicine. DOI: 10.1038/nm.4132
Peidu Jiang, et al. (2014). Cell Research. DOI: 10.1038/cr.2013.161
Ralph A Nixon, et al. (2013). Nature Medicine. DOI: 10.1038/nm.3232
Augustine M.K. Choi, et al. (2013). The New England Journal of Medicine. DOI: 10.1056/NEJMral205406 |
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