GRAMD1C promotes autophagy initiation and mitochondrial bioenergetics through regulation of ER-mitochondria cholesterol transport
Ng, M. Y. W.; Charsou, C.; Lapao, A. S. D. S.; Singh, S.; Trachsel-Moncho, L.; Nakken, S.; Munson, M. J.; Simonsen, A.
Show abstract
During autophagy, cytosolic cargo is sequestered into double-membrane vesicles called autophagosomes. The origin and identity of the membranes that form the autophagosome remain to be fully characterized. Here, we investigated the role of cholesterol in starvation- induced autophagy and identify a role for the ER-localized cholesterol transport protein GRAMD1C in the regulation of autophagy and mitochondrial function. We demonstrate that cholesterol depletion leads to a rapid induction of autophagy, possibly caused by a corresponding increased abundance of curved autophagy membranes. We further show that GRAMD1C is a negative regulator of starvation-induced autophagy. Similar to its yeast orthologue, GRAMD1C is recruited to mitochondria through its GRAM domain. Additionally, we find that GRAMD1C depletion leads to increased mitochondrial cholesterol accumulation and mitochondrial oxidative phosphorylation. Finally, we demonstrate that expression of GRAM family genes is linked to clear cell renal carcinoma survival, highlighting the pathophysiological relevance of cholesterol transport proteins.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- GAK and PRKCD are positive regulators of PRKN-independent mitophagy 98%
- Ca2+-activated sphingomyelin scrambling and turnover mediate ESCRT-independent lysosomal repair 96%
- Quantitative Phosphoproteomic Analyses Identify STK11IP as a Lysosome-Specific Substrate of mTORC1 that Regulates Lysosomal Acidification 96%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Lysosomal degradation ensures accurate chromosomal segregation to prevent genomic instability 96%
- The human vault RNA enhances tumorigenesis and chemoresistance through the lysosome 96%
- Nix induced mitochondrial fission, mitophagy, and myocyte insulin resistance are abrogated by PKA phosphorylation. 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.